Publications by authors named "Lunxu Liu"

265 Publications

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Mar;24(3):141-160

Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing 100142, China.

Background: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).

Methods: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.

Results: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.

Conclusions: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.06DOI Listing
March 2021

Accurate diagnosis of pulmonary nodules using a non-invasive DNA methylation test.

J Clin Invest 2021 Apr 1. Epub 2021 Apr 1.

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Current clinical management of patients with pulmonary nodules involves either repeated LDCT/CT scans or invasive procedures yet causes significant patient misclassification. An accurate non-invasive test is needed to identify malignant nodules and reduce unnecessary invasive tests.

Method: We developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients' plasma samples, and then validated in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules.

Results: A 100-feature model was developed and validated for pulmonary nodule diagnosis: the model achieved a ROC-AUC of 0.843 on 140 independent validation samples with an accuracy of 0.800. The performance was well maintained in, 1) 6-20 mm size subgroup (N=100), with a sensitivity of 1.000 and adjusted NPV of 1.000 at 10% prevalence; 2) stage I malignancy (N=90), with a sensitivity of 0.971; 3) different nodule types - solid nodules (N=78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (N=75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (N=67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and two clinical prediction models (Mayo and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones.

Conclusion: This study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early-stage lung cancer from pulmonary nodule patients and guide clinical decisions.

Funding: The National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.
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http://dx.doi.org/10.1172/JCI145973DOI Listing
April 2021

Identifying the prognostic significance of B3GNT3 with PD-L1 expression in lung adenocarcinoma.

Transl Lung Cancer Res 2021 Feb;10(2):965-980

Department of Thoracic Surgery, Institute of Thoracic Oncology/West China Hospital, Sichuan University, Chengdu, China.

Background: As a novel treatment, programmed cell death protein 1 (PD-1) inhibitor appears to be less effective in tumors of lung adenocarcinoma patients with epidermal growth factor receptor () mutation. Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) has reported to be associated with programmed death ligand 1 (PD-L1)/PD-1 interaction. However, the relationship between B3GNT3 and PD-L1 and its prognostic significance in.

Egfr: mutant status are still unknown.

Methods: B3GNT3 was identified through transcriptome sequencing and The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) database. Flow cytometry and real-time polymerase chain reaction were performed to investigate the association between B3GNT3, PD-L1, and . Then, B3GNT3 and PD-L1 expression were evaluated by immunohistochemical analysis in 145 surgically resected primary lung adenocarcinomas. The relationships between survival and B3GNT3, PD-L1, and status were assessed, and the potential prognostic factors in patients with B3GNT3 expression were identified.

Results: We found that activation induced PD-L1 expression, and EGFR tyrosine kinase inhibitor (TKI) could reduce PD-L1 protein in EGFR-TKI-sensitive HCC827 and PC9 cell lines. Subsequent analysis showed that inhibitor could also lead to both decreased PD-L1 and B3GNT3 mRNA expression. A total of 145 lung adenocarcinoma patients were included. PD-L1 >1% and B3GNT3-positive expression in patients might contribute to worse prognosis in both overall survival (OS) [hazard ratio (HR), 2.63; 95% confidence interval (CI), 0.98-7.06; P=0.048] and disease-free survival (DFS) (HR, 3.04; 95% CI, 1.13-8.14; P=0.019), especially in the PD-L1 ≥50% group. However, when patients were negative for B3GNT3, PD-L1, and (or "triple negative"), there were significant decreases in OS (HR, 5.44; 95% CI, 0.99-29.83; P=0.029) and DFS (HR, 7.24; 95% CI, 1.32-39.73; P=0.008). Positive B3GNT3 expression was a significant risk factor associated with lower DFS (HR, 3.30; P=0.043).

Conclusions: Our results indicate that the B3GNT3 expression is tightly correlated with PD-L1 expression and mutation status. B3GNT3 is associated with poor prognosis in lung adenocarcinoma patients. Collectively, these findings may offer new insight into enhancing immune therapy efficacy for lung adenocarcinoma patients.
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http://dx.doi.org/10.21037/tlcr-21-146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947420PMC
February 2021

Clinicopathological features and prognostic analysis of metastatic pulmonary sarcomatoid carcinoma: a SEER analysis.

J Thorac Dis 2021 Feb;13(2):893-905

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare type of non-small cell lung cancer (NSCLC). Metastases are often detected at the first diagnosis. Despite high rates of distant metastasis, there is insufficient data describing the characteristics of PSC metastasis.

Methods: We performed a Surveillance, Epidemiology, and End Results (SEER) database-based analysis of clinicopathological features and prognosis of distant metastasis in PSC patients. Data queried for this analysis included PSC patients in the database between 2010 and 2016.

Results: A total of 934 patients met the criteria for inclusion in the analysis and included, at the time of diagnosis, 512 (54.8%) patients with metastasis, including bone (n=152; 16.3%), brain (n=108; 11.6%), liver (n=70; 7.5%), lung (n=142; 15.2%) metastases. Binary logistic regression showed that patients with giant cell carcinoma [odds ratio (OR) 4.023, 95% confidence interval (CI): 2.113-7.661, P<0.001] and spindle cell carcinoma (OR 3.151, 95% CI: 1.699-5.843, P<0.001) were associated with metastasis. Log-rank test and Kaplan-Meier plots indicated poor prognosis in metastatic patients [the 1-, 3-, and 5-year overall survival (OS) rates were 14.1%, 5.5%, and 4.8%, respectively]. Multivariable analysis showed younger and chemotherapy as improved prognostic factors of PSC patients with single metastasis site.

Conclusions: The SEER database-based analysis revealed the clinical features of distant metastasis of PSC and showed that different histological types posed distinct metastasis potential. Besides, age and chemotherapy were the independent prognostic factors of PSC patients with single metastasis site.
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http://dx.doi.org/10.21037/jtd-20-2826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947519PMC
February 2021

Skip metastasis in mediastinal lymph node is a favorable prognostic factor in N2 lung cancer patients: a meta-analysis.

Ann Transl Med 2021 Feb;9(3):218

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Skip metastasis is a common lymph node metastatic pattern in non-small cell lung cancer (NSCLC). The relationship between skip metastasis and specific clinicopathologic factors and the prognostic value of skip metastasis are controversial.

Methods: A systematic search and analysis of skip metastasis in NSCLC was conducted in the databases of PubMed, EMBASE, and Web of Science up to Dec 2019. Summarized hazard ratio (HR), mean difference (MD), and odds ratio (OR) with associated 95% confidence intervals (CI) were evaluated to investigating the relationship between skip metastasis and overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and clinicopathological features in NSCLC.

Results: 29 studies with a total of 1,806 skip and 4,670 non-skip N2 patients were included. The upper lobe tumor showed a higher rate of skip metastasis compared with lower lobe one (RR =1.16, 95% CI: 1.00-1.34, P=0.044, I=39.8%). The presence of skip metastasis correlated with superior overall survival (HR =0.74, 95% CI: 0.66-0.83, P<0.001, I=48.2%) and DFS or RFS (HR =0.71, 95% CI: 0.61-0.84, P<0.001, I=18.2%). Further subgroup analyses indicated similar results in articles that reported intrapulmonary lymph node dissection (HR =0.67, 95% CI: 0.57-0.77, P<0.001, I=0).

Conclusions: The results indicate that the presence of skip metastasis is associated with a marked increase in survival of NSCLC patients compared to patients with non-skip N2 metastasis. These results suggest that skip metastasis might be a distinct subgroup for purposes of N staging of NSCLC patients, and intrapulmonary lymph node assessment is needed.
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http://dx.doi.org/10.21037/atm-20-3513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940896PMC
February 2021

Effect of patient-controlled intravenous analgesia combined with flurbiprofen axetil and dezocine on postoperative analgesia for lobectomy (EPIC-FAD): a trial protocol.

Trials 2021 Mar 1;22(1):175. Epub 2021 Mar 1.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.

Background: The optimal analgesic strategy for surgical pain after lobectomy remains undefined. To compare the combination of flurbiprofen axetil and dezocine with flurbiprofen axetil alone and dezocine alone, in post-lobectomy patients.

Methods: A single-center, parallel-design double-blind superiority trial, with 5 groups (1:1:1:1:1 ratio) with different combinations of flurbiprofen and dezocine. Patients scheduled for lobectomy will be recruited. The primary outcome is total sufentanil use in patient-controlled intravenous analgesia within the first 24 postoperative hours. Secondary outcomes include pain numeric rating scales at 6th, 12th, 24th, 48th, and 72th postoperative hours, and on the 1st, 3rd, and 6th postoperative months at rest and during coughing, adverse effects from experimental drug treatment, sufentanil use at other time points, analgesia cost, time to chest tube removal, length of hospital stay, time to pass first flatus, and serum level of cytokines. Doctors, patients, and nurses are blinded, and only the manager is unblinded. Analysis is intention-to-treat. Statistical analysis is pre-specified. Statistical comparison of the treatment groups includes one-way analysis of variance followed by Tukey's post hoc test.

Discussion: Trial did not begin to recruit. Participant recruitment start date is planned to be June 1, 2020. Approximate recruitment end date is May 31, 2021. If successful, the trial may shed light on the use of certain analgesic combinations in post-lobectomy pain control.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800018563 . Registered on September 25, 2018.
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http://dx.doi.org/10.1186/s13063-021-05108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923454PMC
March 2021

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.

Ann Med 2021 12;53(1):391-401

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.

Method: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.

Results: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81,  = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days ( = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days ( = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.

Conclusions And Relevance: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
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http://dx.doi.org/10.1080/07853890.2021.1890329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906612PMC
December 2021

Perioperative comparison of video-assisted thoracic surgery and open lobectomy for pT1-stage non-small cell lung cancer patients in China: a multi-center propensity score-matched analysis.

Transl Lung Cancer Res 2021 Jan;10(1):402-414

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Compared with open surgery, video-assisted thoracic surgery (VATS) has innovated the concept of the minimally invasive approach for non-small cell lung cancer (NSCLC) patients in past decades. This present study aimed to compare the perioperative and lymph node dissection outcomes between VATS lobectomy and open lobectomy for pathological stage T1 (pT1) NSCLC patients from both surgical and oncologic perspectives.

Methods: This was a retrospective multicenter study. Patients who underwent surgical resection for pT1 NSCLC between January 2014 and September 2017 were retrospectively reviewed from 10 thoracic surgery centers in China. Perioperative and lymph node dissection outcomes of pT1 NSCLC patients who accepted VATS or open lobectomies were compared by propensity score matching (PSM) analysis.

Results: Of the 11,360 patients who underwent surgery for pT1 NSCLC, 7,726 were enrolled based on the selection criteria, including 1,222 cases of open lobectomies and 6,504 cases of VATS lobectomies. PSM resulted in 1,184 cases of open lobectomies and 1,184 cases of VATS lobectomies being well matched by common prognostic variables, including age, sex, and surgical side. VATS lobectomy led to better perioperative outcomes, including less blood loss (133.5±200.1 233.3±318.4, P<0.001), lower blood transfusion rate (2.4% 6.4%, P<0.001), shorter postoperative hospital stay (8.6±5.7 10.1±5.1, P<0.001), less chest drainage volume (1,109.5±854.0 1,324.1±948.8, P<0.001), and less postoperative complications (4.9% 8.2%, P<0.001). However, open lobectomy had better lymph node dissection outcomes than VATS, with increased lymph node dissection numbers (16.1±9.4 13.7±7.7, P<0.001) and more positive lymph nodes being dissected (1.5±3.9 1.1±2.5, P=0.002). Compared with VATS, open lobectomy harvested more lymph node stations (5.5±1.9 5.2±1.8, P=0.001), including more pathological N2 (pN2) lymph node stations (3.4±1.4 3.1±1.3, P<0.001).

Conclusions: VATS lobectomy was associated with better perioperative outcomes, such as less blood loss, lower blood transfusion rate, shorter postoperative hospital stay, less chest drainage volume and less postoperative complications. Open lobectomy has improved lymph node dissection outcomes, as more lymph nodes and positive lymph nodes were dissected for pT1 NSCLC patients during surgery.
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http://dx.doi.org/10.21037/tlcr-20-1132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867771PMC
January 2021

SurvNet: A Novel Deep Neural Network for Lung Cancer Survival Analysis With Missing Values.

Front Oncol 2020 20;10:588990. Epub 2021 Jan 20.

Machine Intelligence Laboratory, College of Computer Science, Sichuan University, Chengdu, China.

Survival analysis is important for guiding further treatment and improving lung cancer prognosis. It is a challenging task because of the poor distinguishability of features and the missing values in practice. A novel multi-task based neural network, SurvNet, is proposed in this paper. The proposed SurvNet model is trained in a multi-task learning framework to jointly learn across three related tasks: input reconstruction, survival classification, and Cox regression. It uses an input reconstruction mechanism cooperating with incomplete-aware reconstruction loss for latent feature learning of incomplete data with missing values. Besides, the SurvNet model introduces a context gating mechanism to bridge the gap between survival classification and Cox regression. A new real-world dataset of 1,137 patients with IB-IIA stage non-small cell lung cancer is collected to evaluate the performance of the SurvNet model. The proposed SurvNet achieves a higher concordance index than the traditional Cox model and Cox-Net. The difference between high-risk and low-risk groups obtained by SurvNet is more significant than that of high-risk and low-risk groups obtained by the other models. Moreover, the SurvNet outperforms the other models even though the input data is randomly cropped and it achieves better generalization performance on the Surveillance, Epidemiology, and End Results Program (SEER) dataset.
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http://dx.doi.org/10.3389/fonc.2020.588990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855857PMC
January 2021

Automatic airway tree segmentation based on multi-scale context information.

Int J Comput Assist Radiol Surg 2021 Feb 19;16(2):219-230. Epub 2021 Jan 19.

Machine Intelligence Laboratory, College of Computer Science, Sichuan University, Chengdu, 610065, People's Republic of China.

Purpose: Airway tree segmentation plays a pivotal role in chest computed tomography (CT) analysis tasks such as lesion localization, surgical planning, and intra-operative guidance. The remaining challenge is to identify small bronchi correctly, which facilitates further segmentation of the pulmonary anatomies.

Methods: A three-dimensional (3D) multi-scale feature aggregation network (MFA-Net) is proposed against the scale difference of substructures in airway tree segmentation. In this model, the multi-scale feature aggregation (MFA) block is used to capture the multi-scale context information, which improves the sensitivity of the small bronchi segmentation and addresses the local discontinuities. Meanwhile, the concept of airway tree partition is introduced to evaluate the segmentation performance at a more granular level.

Results: Experiments were conducted on a dataset of 250 CT scans, which were annotated by experienced clinical radiologists. Through the airway partition, we evaluated the segmentation results of the small bronchi compared with the state-of-the-art methods. Experiments show that MFA-Net achieves the best performance in the Dice similarity coefficient (DSC) in the intra-lobar airway and improves the true positive rate (TPR) by 7.59% on average. Besides, in the entire airway, the proposed method achieves the best results in DSC and TPR scores of 86.18% and 79.31%, respectively, with the consequence of higher false positives.

Conclusion: The MFA-Net is competitive with the state-of-the-art methods. The experiment results indicate that the MFA block improves the performance of the network by utilizing multi-scale context information. More accurate segmentation results will be more helpful in further clinical analysis.
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http://dx.doi.org/10.1007/s11548-020-02293-xDOI Listing
February 2021

Thymic Squamous Cell Carcinoma: A Population-Based Surveillance, Epidemiology, and End Result Analysis.

Front Oncol 2020 22;10:592023. Epub 2020 Dec 22.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Objectives: Thymic squamous cell carcinoma (TSCC) is a rare neoplasm that has been sparsely cited in the literature. The aim of this study was to determine disease characteristics and prognostic factors of patients in a Surveillance, Epidemiology, and End Results (SEER) analysis.

Methods: Cases from 1990-2016 were retrieved from the SEER database and demographics, treatments, and survival outcomes were analyzed.

Results: The TSCC accounted for 72.4% of the thymic carcinomas and 7.2% of thymic tumors. The 276 patients (165 men) selected for analysis had a median age of 65 (24-85) years, and 201 patients were diagnosed with Masaoka-Koga stage III/IV. The median survival of TSCC was 59 months with a 49.0% 5-year OS rate, a better prognosis than lymphoepithelioma-like carcinoma (32.1%) and undifferentiated carcinoma (33.3%). Multivariate analysis revealed the Masaoka-Koga stage (p = 0.003) and surgical types (complete resection, incomplete resection, and none; p < 0.001) were determinants of survival. Complete resection had the best prognosis with a 72.7% 5-year OS rate. Chemotherapy was an independent protective factor (HR = 0.555, 95% CI 0.347-0.886; p = 0.014) though poor survival was showed in univariate analysis. And the survival benefit of chemotherapy was validated in PSM analysis (3-year OS rate was 77.7% with chemotherapy 52.8% without chemotherapy; p = 0.014).

Conclusions: TSCC was frequently diagnosed in older patients with advanced Masaoka-Koga stage and had more favorable survival than other subtypes of thymic carcinomas. Complete resection is the preferred treatment. Masaoka-Koga stage and chemotherapy had a strong association with prognosis.
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http://dx.doi.org/10.3389/fonc.2020.592023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783386PMC
December 2020

Lobe-Specific Node Dissection Can Be a Suitable Alternative to Systematic Lymph Node Dissection in Highly Selective Early-Stage Non-Small-Cell Lung Cancer Patients: A Meta-Analysis.

Ann Thorac Cardiovasc Surg 2020 Dec 7. Epub 2020 Dec 7.

West China School of Medicine, Sichuan University, Chengdu, China.

Purpose: Whether the lobe-specific lymph node dissection is an alternative to systematic lymph node dissection for early-stage non-small-cell lung cancer remains controversial. An elaborate meta-analysis was conducted to evaluate the effects of lobe-specific lymph node dissection in early-stage patients.

Methods: A systematic literature search was conducted up to February 19, 2020 in PubMed, Ovid, Web of Science, and China National Knowledge Infrastructure databases. The outcomes including overall survival (OS), complications, and recurrence rate were extracted and analyzed.

Results: Nine studies including one randomized controlled trial (RCT) and eight retrospective cohort studies with 8499 non-small-cell lung cancer patients were included. The results indicated that lobe-specific lymph node had a lower rate of postoperative complication (relative risk [RR]: 0.83, 95% confidence interval [CI]: 0.72-0.95, P = 0.006). No significant difference was observed between lobe-specific lymph node and systematic lymph node dissection in OS (hazard rate = 1.12, 95% CI: 0.81-1.54, P = 0.501) with high heterogeneity (I = 71.9%).

Conclusion: Lobe-specific lymph node can reach a comparable long-term prognosis in some highly selected patients. However, these results should be viewed cautiously with the existence of high heterogeneity. Due to the high heterogeneity, a strict patient selection process by experienced thoracic surgeons was recommended before validating lobe-specific lymph node.
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http://dx.doi.org/10.5761/atcs.oa.20-00136DOI Listing
December 2020

Prognostic significance of the N1 classification pattern: a meta-analysis of different subclassification methods.

Eur J Cardiothorac Surg 2021 Apr;59(3):545-553

West China School of Medicine, Sichuan University, Chengdu, China.

Objectives: The number of positive lymph node stations has been viewed as a subclassification in the N1 category in the new revision of tumour node metastasis (TNM) staging. However, the survival curve of these patients overlapped with that of some patients in the N2 categories. Our study focused on the prognostic significance of different subclassifications for N1 patients.

Methods: We systematically searched PubMed, Ovid, Web of Science and the Cochrane Library on the topic of N1 lymph node dissection. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were used to assess the prognostic significance of N1 metastases. I2 statistics was used to evaluate heterogeneity among the studies: If significant heterogeneity existed (P ≤ 0.10; I2 >50%), a random effect model was adopted.

Results: After a careful investigation, a total of 17 articles were included in the analysis. The results showed that patients with non-small-cell lung cancer with multistation N1 disease have worse survival compared with those with single-station N1 disease (HR 1.53, 95% CI 1.32-1.77; P < 0.001; I2 = 5.1%). No significant difference was observed between groups when we assessed the number of positive lymph nodes (single or multiple) (HR 1.25, 95% CI 0.96-1.64; P = 0.097; I2 = 72.5%). Patients with positive hilar zone lymph nodes had poorer survival than those limited to the intrapulmonary zone (HR 1.80, 95% CI 1.57-2.07; P < 0.001; I2 = 0%). A subgroup analysis conducted according to the different validated lymph node maps showed a stable result.

Conclusions: Our result confirmed the prognostic significance of the N1 subclassification based on station number. Meanwhile, location-based classifications, especially zone-based, were also identified as prognostically significant, which may need further confirmation and validation in the staged population.
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http://dx.doi.org/10.1093/ejcts/ezaa388DOI Listing
April 2021

KRAS G12C mutations in Asia: a landscape analysis of 11,951 Chinese tumor samples.

Transl Lung Cancer Res 2020 Oct;9(5):1759-1769

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Kirsten rat sarcoma vial oncogene () is one of the most prevalent oncogenes in multiple cancer types, but the incidence is different between the Asian and non-Asian populations. The recent development of G12C targeting drug has shown great promise. It is thus important to understand the genomic landscape of G12C in a specific population.

Methods: Sequencing data of 11,951 tumor samples collected from 11/2016 to 7/2019 from multiple centres in China were analyzed for mutation status. Concomitant genomic aberrations were further analyzed in tumors with G12C mutations, which were sequenced with comprehensive cancer panel including over 450 cancer-related genes. Smoking status and its correlation with were analyzed in 2,235 lung cancer cases within this cohort.

Results: KRAS mutations were identified in 1978 (16.6%) patient samples. Specifically, G12C accounted for 14.5% (n=286) of all mutations. G12C was most commonly seen in lung cancer (4.3%), followed by colorectal cancer (2.5%) and biliary cancer (2.3%). Almost all patients (99.6%) with G12C mutations had concomitant genomic aberrations. These were most commonly associated with the RAS/RTK pathway including and mutations. Moreover, mutation was positively correlated with smoking status in lung adenocarcinomas.

Conclusions: The overall incidence of G12C mutations remains low in the Chinese population. The most common tumor types harboring G12C mutations are in patients suffering from lung, colorectal and biliary cancers.
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http://dx.doi.org/10.21037/tlcr-20-455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653137PMC
October 2020

Video-assisted thoracoscopic surgery lobectomy might be a feasible alternative for surgically resectable pathological N2 non-small cell lung cancer patients.

Thorac Cancer 2021 01 18;12(1):21-29. Epub 2020 Nov 18.

Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Background: The majority of previous studies of the clinical outcome of video-assisted thoracoscopic surgery (VATS) versus open lobectomy for pathological N2 non-small cell lung cancer (pN2 NSCLC) have been single-center experiences with small patient numbers. The aim of this study was therefore to investigate these procedures but in a large cohort of Chinese patients with pathological N2 NSCLC in real-world conditions.

Methods: Patients who underwent lobectomy for pN2 NSCLC by either VATS or thoracotomy were retrospectively reviewed from 10 tertiary hospitals between January 2014 and September 2017. Perioperative outcomes and overall survival of the patients were analyzed. Cox regression analysis was performed to identify potential prognostic factors. Propensity-score analysis was performed to reduce cofounding biases and compare the clinical outcomes between both groups.

Results: Among 2144 pN2 NSCLC, 1244 patients were managed by VATS and 900 by open procedure. A total of 305 (24.5%) and 344 patients died during VATS and the thoracotomy group during a median follow-up of 16.7 and 15.6 months, respectively. VATS lobectomy patients had better overall survival when compared with those undergoing the open procedure (P < 0.0001). Multivariate COX regression analysis showed VATS lobectomy independently favored overall survival (HR = 0.75, 95% CI: 0.621-0.896, P = 0.0017). Better perioperative outcomes, including less blood loss, shorter drainage time and hospital stay, were also observed in patients undergoing VATS lobectomy (P < 0.05). After propensity-score matching, 169 patients in each group were analyzed, and no survival difference were found between the two groups. Less blood loss was observed in the VATS group, but there was a longer operation time.

Conclusions: VATS lobectomy might be a feasible alternative to conventional open surgery for resectable pN2 NSCLC.

Key Points: Significant findings of the study: VATS lobectomy has comparative OS in pN2 NSCLC versus open procedure in resectable patients.

What This Study Adds: VATS lobectomy might be feasible for pN2 NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779187PMC
January 2021

The Favorable Prognostic Factors for Superior Sulcus Tumor: A Systematic Review and Meta-Analysis.

Front Oncol 2020 20;10:561935. Epub 2020 Oct 20.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Superior sulcus tumor is a rare non-small cell lung cancer with poor prognosis. Exploring the potential prognostic factors of patients with superior sulcus tumor and adopting individualized treatment for patients with different prognostic factors are of great significance for the prolongation of patients' lives. To figure out the prognostic factors of upper sulcus tumors, a meta-analysis was conducted. We searched all the articles published until January 2020 in PubMed, Embase, and Web of Science databases, and the search strategy included the following terms, combining superior sulcus tumor and prognosis. Hazard ratio (HR) with associated confidential interval (CI) was evaluated for the purpose of investigating prognostic factors for superior sulcus tumor. STATA 16.0 was used for analysis of extracted data and assessment of publication bias. Fifteen eligible studies, which had 1,009 patients with superior sulcus tumor, were included in this meta-analysis. The studies were published between 1994 and 2018, and the patient recruitment periods ranged from 1974 to 2016. The median follow-up time ranged from 18 to 95 months. The meta-analysis indicated that lower T stage (HR, 1.63; 95% CI, 1.35-1.97), lower N stage (HR, 3.08; 95% CI: 2.37-3.99), negative surgical margin (HR, 0.25; 95% CI, 0.17-0.38), and pathologic complete response (HR, 0.55; 95% CI, 0.39-0.77) were favorable prognostic factors. We found that T stage, N stage, surgical margin, and pathologic complete response are prognostic factors for superior sulcus tumor. To reach a better long-term survival, patients with these negative prognostic factors may need a more aggressive treatment, while more studies should be conducted to further validate these results and explore a more effective treatment.
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http://dx.doi.org/10.3389/fonc.2020.561935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606951PMC
October 2020

ROS1-fusion protein induces PD-L1 expression via MEK-ERK activation in non-small cell lung cancer.

Oncoimmunology 2020 05 6;9(1):1758003. Epub 2020 May 6.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Introduction: Despite some of the oncogenic driver mutations that have been associated with increased expression of programmed death-ligand 1 (PD-L1), the correlation between PD-L1 expression and ROS1 fusion in NSCLC cells, especially for those with Crizotinib resistance has not been fully addressed.

Materials And Methods: The expression of PD-L1 in 30 primary NSCLC tumors with/without ROS1-fusion protein was evaluated by immunohistochemical (IHC) analysis. To assess the correlation between ROS1 fusion and PD-L1 expression, we down-regulated ROS1 with RNA interference or specific inhibitor (Crizotinib) in ROS1-fusion positive NSCLC cell line HCC78; or up-regulate ROS1-fusion gene in an immortalized human bronchial epithelial cell line (HBE). Mouse xenograft models were also used to determine the effect of ROS1 expression on PD-L1 expression . Crizotinib-resistant cell line was generated for measuring the association between Crizotinib resistance and PD-L1 expression.

Results: ROS1-rearrangement in primary NSCLC tumor was significantly associated with up-regulated PD-L1 expression. PD-L1 expression was significantly up-regulated in bronchial epithelial cells after forced expression of ROS1 fusion and was eliminated when HCC78 xenograft mouse models were treated with Crizotinib. We found PD-L1 expression was modulated by MEK-ERK pathway signaling in both parental and Crizotinib-resistant NSCLC cells with ROS1 fusion.

Conclusions: The correlation between ROS1-fusion and PD-L1 overexpression suggested that PD-L1/PD-1 blockade could be the second-line treatment option for the Crizotinib-resistant NSCLC with rearrangement.
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http://dx.doi.org/10.1080/2162402X.2020.1758003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458663PMC
May 2020

LncAS2Cancer: a comprehensive database for alternative splicing of lncRNAs across human cancers.

Brief Bioinform 2020 Aug 21. Epub 2020 Aug 21.

Department of Thoracic Surgery, West China Hospital, Sichuan University.

Accumulating studies demonstrated that the roles of lncRNAs for tumorigenesis were isoform-dependent and their aberrant splicing patterns in cancers contributed to function specificity. However, there is no existing database focusing on cancer-related alternative splicing of lncRNAs. Here, we developed a comprehensive database called LncAS2Cancer, which collected 5335 bulk RNA sequencing and 1826 single-cell RNA sequencing samples, covering over 30 cancer types. By applying six state-of-the-art splicing algorithms, 50 859 alternative splicing events for 8 splicing types were identified and deposited in the database. In addition, the database contained the following information: (i) splicing patterns of lncRNAs under seven different conditions, such as gene interference, which facilitated to infer potential regulators; (ii) annotation information derived from eight sources and manual curation, to understand the functional impact of affected sequences; (iii) survival analysis to explore potential biomarkers; as well as (iv) a suite of tools to browse, search, visualize and download interesting information. LncAS2Cancer could not only confirm the known cancer-associated lncRNA isoforms but also indicate novel ones. Using the data deposited in LncAS2Cancer, we compared gene model and transcript overlap between lncRNAs and protein-coding genes and discusses how these factors, along with sequencing depth, affected the interpretation of splicing signals. Based on recurrent signals and potential confounders, we proposed a reliable score to prioritize splicing events for further elucidation. Together, with the broad collection of lncRNA splicing patterns and annotation, LncAS2Cancer will provide important new insights into the diverse functional roles of lncRNA isoforms in human cancers. LncAS2Cancer is freely available at https://lncrna2as.cd120.com/.
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http://dx.doi.org/10.1093/bib/bbaa179DOI Listing
August 2020

Naples Prognostic Score as a novel prognostic prediction tool in video-assisted thoracoscopic surgery for early-stage lung cancer: a propensity score matching study.

Surg Endosc 2020 Aug 3. Epub 2020 Aug 3.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.

Backgrounds: The Naples Prognostic Score (NPS) emerges as a novel prognostic scoring system in surgical oncology. We aim to assess the prognostic significance of preoperative NPS in patients undergoing completely video-assisted thoracoscopic surgery (VATS) lobectomy for early-stage non-small cell lung cancer (NSCLC) by propensity score matching (PSM) analysis.

Methods: The present study was conducted on our single-center prospectively maintained database between January 2014 and December 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative NPS. Finally, multivariable Cox-proportional hazards regression analysis and PSM analysis were carried out to determine the independent prognostic factors for both OS and DFS.

Results: There were 457 patients with operable primary stage I-II NSCLC included. Per 1-point increase in NPS was found to be significantly associated with unfavorable OS and DFS of NSCLC. Both OS and DFS were significantly shortened along with each number increase in the NPS group, showing a step-wise fashion. Such strong correlations between preoperative NPS and survival outcomes still remained validated after PSM analysis. In addition, NPS held the best discriminatory power for predicting both OS and DFS when compared to the other peripheral biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that preoperative NPS could be an independent prognostic indicator for both OS and DFS.

Conclusions: The NPS scoring system can serve as a novel risk stratification tool to refine prognostic prediction after VATS lobectomy for surgically resected NSCLC.
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http://dx.doi.org/10.1007/s00464-020-07851-7DOI Listing
August 2020

ASO Author Reflections: Individualized Mediastinal Lymph Node Dissection for Lung Cancer: Do Not Neglect Station 3A Lymph Node.

Ann Surg Oncol 2020 Dec 20;27(Suppl 3):846-847. Epub 2020 Jul 20.

Department of Thoracic Surgery, West China Hospital, Chengdu, Sichuan, China.

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http://dx.doi.org/10.1245/s10434-020-08876-xDOI Listing
December 2020

Comparison of the Short- and Long-term Outcomes of Video-assisted Thoracoscopic Surgery versus Open Thoracotomy Bronchial Sleeve Lobectomy for Central Lung Cancer: A Retrospective Propensity Score Matched Cohort Study.

Ann Surg Oncol 2020 Oct 8;27(11):4384-4393. Epub 2020 Jul 8.

Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, People's Republic of China.

Purpose: The purpose of this study was to evaluate the short- and long-term outcomes of video-assisted thoracoscopic surgery (VATS) versus open thoracotomy bronchial sleeve lobectomy (BSL) for patients with central lung cancer.

Methods: This is a retrospective cohort study. Perioperative outcomes and long-term survival of patients who underwent VATS versus open thoracotomy BSL for central lung cancer from June 2010 and June 2018 in the Western China Lung Cancer Database were compared using propensity score matching (PSM) between the two surgical approaches.

Results: The retrospective study included 187 patients who divided into VATS group (n = 44) and open group (n = 143) according to surgical approach, and PSM resulted in 43 patients in each group, which were well matched by 11 potential prognostic factors. The VATS group was associated with lower overall incidence of postoperative complications (20.3% vs. 30.2%, P = 0.029), less postoperative drainage (875 ml [250-3960] vs. 1280 ml [100-4890], P = 0.039). The 5-year overall survival (OS) and disease-free survival (DFS) were comparable between the VATS and open groups (55.9% vs. 65.2% P = 0.836 and 54.1% vs. 60.2% P = 0.391, respectively) after matching. Multivariable adjusted analysis demonstrated that the surgical approach was not an independent favorable prognostic factor for OS (hazard ratio [HR] = 0.922; 95% confidence interval [CI], 0.427-1.993; P = 0.836) but just the pTNM stage (HR = 2.003; 95% CI 1.187-3.382; P = 0.009).

Conclusions: VATS BSL may achieve equivalent long-term outcomes for central lung cancer patients when comparing with open thoracotomy. Although slightly longer duration of surgery, VATS approach may be a feasible option for lung cancer patients requiring BSL.
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http://dx.doi.org/10.1245/s10434-020-08805-yDOI Listing
October 2020

Clinical Significance of Station 3A Lymph Node Dissection in Patients with Right-Side Non-Small-Cell Lung Cancer: A Retrospective Propensity-Matched Analysis.

Ann Surg Oncol 2021 Jan 7;28(1):194-202. Epub 2020 Jul 7.

Department of Thoracic Surgery, West China Hospital, Chengdu, Sichuan, China.

Purpose: To investigate the prognostic impact of station 3A lymph node (LN) dissection in patients with right-side non-small-cell lung cancer (NSCLC).

Patients And Methods: We retrospectively reviewed data of 1906 patients with primary right-side NSCLC who underwent lobectomy between January 2005 and December 2017 (570 patients underwent station 3A LN dissection and 1336 patients did not). Propensity score matching was conducted to minimize the effects of potential confounding factors. Disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: The metastasis rate of station 3A LN was 15.3% (87/570), which was second only to station 4 (17.3%). Only stations 10 and 11 LN metastases were found to be independent risk factors for station 3A LN metastasis (odds ratio = 19.43, 95% CI 1.21-311.12; P = 0.036 and odds ratio = 53.28, 95% CI 2.02-1404.90; P = 0.016, respectively). After propensity score matching, patients with dissection of station 3A LNs showed higher DFS (5-year DFS, 52.4% vs. 37.1%; P = 0.001) and OS (5-year OS, 58.8% vs. 48.7%; P = 0.007) than those without dissection. Subgroup analysis indicated that station 3A LN dissection was associated with significantly higher DFS and OS in patients with stage II and III disease. In multivariate survival analysis, dissection of 3A LNs retained its independent favorable effect on both DFS (hazard ratio = 0.76, 95% CI 0.64-0.90; P = 0.001) and OS (hazard ratio = 0.73, 95% CI 0.60-0.88; P = 0.001).

Conclusion: Station 3A LN involvement was not rare and station 3A LN dissection was associated with a more favorable prognosis in patients with right-side NSCLC.
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http://dx.doi.org/10.1245/s10434-020-08786-yDOI Listing
January 2021

Chylothorax after Lung Cancer Surgery: A Key Factor Influencing Prognosis and Quality of Life.

Ann Thorac Cardiovasc Surg 2020 Dec 2;26(6):303-310. Epub 2020 Jul 2.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Chylothorax is caused by the accumulation of chylous fluid in the pleural cavity due to the injury of the thoracic duct or its tributaries. Chylothorax following lung cancer surgery, especially pulmonary resection and mediastinal lymph node dissection, is a raw potential postoperative complication as previously reported. Chylothorax might lead to a high mortality rate if not addressed in a timely fashion. This article reviews the anatomy of the thoracic duct, risk factors of postoperative chylothorax, diagnoses and management with chylothorax, and intraoperative prevention of chylothorax. With the development of researches on postoperative chylothorax, more effective treatment and prevention measures need to be proposed to better solve this clinical problem.
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http://dx.doi.org/10.5761/atcs.ra.20-00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801173PMC
December 2020

Clinical significance of tumour mutation burden in immunotherapy across multiple cancer types: an individual meta-analysis.

Jpn J Clin Oncol 2020 Sep;50(9):1023-1031

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Biomarkers for stratifying patients that could benefit from immune checkpoint inhibitors are necessary. Tumour mutation burden has recently become a promising biomarker in cancer, but the associations between tumour mutation burden and outcomes of immune checkpoint inhibitors treatment were not well-documented in present studies.

Methods: We searched PubMed, Web of Science and EMBASE databases up to 1 October 2019. Studies evaluated the association between tumour mutation burden and clinical outcomes were included. Hazard ratios and odds ratios were applied to estimate the association of tumour mutation burden score with overall survival, progression-free survival and response rate, respectively. The best cut-off value was chosen by best discriminated overall survival using Contal and O'Quigley method.

Results: Twenty-two studies involving 6171 patients in diverse cancers were included. The individual participant data meta-analysis demonstrated that high tumour mutation burden was associated with better overall survival (HR = 0.57, 95% CI = 0.50-0.64) and progression-free survival (HR = 0.50, 95% CI = 0.40-0.63) and higher response rate. The best cut-off values in each cancer type were 17.7/MB in non-small cell lung cancer, 7.9/MB in bladder cancer, 6.1/MB in melanoma, 12.3/MB in colorectal cancer, 6.9/MB in esophagogastric cancer, 10.5/MB in head and neck cancer. The pooled meta-analysis showed the prognosis value was robust and the sensitivity, specificity and area under the receiver operating characteristic curves in predicting response rates were 0.63, 0.71 and 0.73, respectively.

Conclusions: The present meta-analysis indicates tumour mutation burden is a promising predictor of immune checkpoint inhibitors therapy but the cut-off value differs in different cancers.
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http://dx.doi.org/10.1093/jjco/hyaa076DOI Listing
September 2020

miR-410 induces both epithelial-mesenchymal transition and radioresistance through activation of the PI3K/mTOR pathway in non-small cell lung cancer.

Signal Transduct Target Ther 2020 06 12;5(1):85. Epub 2020 Jun 12.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.

Radiotherapy remains one of the major treatments for non-small cell lung cancer (NSCLC) patients; whereas intrinsic or acquired radioresistance limits its efficacy. Nevertheless, most studies so far have only focused on acquired resistance. The exact mechanisms of intrinsic radioresistance in NSCLC are still unclear. A few studies have suggested that epithelial-mesenchymal transition (EMT) is associated with radioresistance in NSCLC. However, little is known about whether the abnormal expression of specific microRNAs induces both EMT and radioresistance. We previously found that miR-410 has multiple roles as an oncomiRNA in NSCLC. In this study, we revealed that miR-410 overexpression promoted EMT and radioresistance, accompanied by enhanced DNA damage repair both in vitro and in vivo. Conversely, knockdown of miR-410 showed the opposite effects. We further demonstrated that PTEN was a direct target of miR-410 by using bioinformatic tools and dual-luciferase reporter assays, and the miR-410-induced EMT and radioresistance were reversed by PI3K, Akt, and mTOR inhibitors or by restoring the expression of PTEN in NSCLC cells. In addition, we preliminarily found that the expression of miR-410 was positively correlated with EMT and negatively associated with the expression of PTEN in NSCLC specimens. In summary, these results demonstrated that miR-410 is an important regulator on enhancing both NSCLC EMT and radioresistance by targeting the PTEN/PI3K/mTOR axis. The findings suggest that miR-410-induced EMT might significantly contribute to the enhanced radioresistance. Therefore, miR-410 may serve as a potential biomarker or therapeutic target for NSCLC radiotherapy.
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http://dx.doi.org/10.1038/s41392-020-0182-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290026PMC
June 2020

Thoracic surgeons' insights: Improving thoracic surgery outcomes during the Coronavirus Disease 2019 pandemic.

J Thorac Cardiovasc Surg 2020 08 4;160(2):597-600. Epub 2020 Jun 4.

Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.04.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271864PMC
August 2020

Thoracic Surgeons' Insights: Improving Thoracic Surgery Outcomes During the Coronavirus Disease 2019 Pandemic.

Ann Thorac Surg 2020 08 4;110(2):349-352. Epub 2020 Jun 4.

Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.athoracsur.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271845PMC
August 2020

Thoracic surgeons' insights: Improving thoracic surgery outcomes during the Coronavirus Disease 2019 pandemic.

Eur J Cardiothorac Surg 2020 08;58(2):207-209

Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1093/ejcts/ezaa214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314075PMC
August 2020

SKA1/2/3 serves as a biomarker for poor prognosis in human lung adenocarcinoma.

Transl Lung Cancer Res 2020 Apr;9(2):218-231

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Background: Spindle and kinetochore associated complex subunit 1/2/3 (SKA1/2/3), which stabilized spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis, were dysregulated, and closely related to prognosis in several malignant tumors. Nevertheless, the potential clinical value of SKA1/2/3, especially in terms of prognosis and development of NSCLC, had not been fully elucidated.

Methods: ONCOMINE, GEPIA, UALCAN, TCGA, STRING and other databases were used to analyze the expression of SKA1/2/3 in patients with lung adenocarcinoma (LUAD) and its clinical value, and to explore the possible regulatory mechanism of SKA in the occurrence and development of LUAD.

Results: In patients with LUAD, SKA1/2/3 mRNA expression level was significantly up-regulated, and AUC was 0.9558, 0.7034 and 0.9775, respectively. Increased SKA 1/2/3 expression was associated with smoking, tissue typing, and poor prognosis in LUAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed that SKA1/2/3 was mainly enriched in DNA replication, cell cycle, homologous recombination, p53 signaling pathway, etc. Hub genes in protein-protein interactions are CDK1, BUB1, CCNA2, CDC20, CCNB2, CCNB1, BUB1B, AURKB, TOP2A and MAD2L1. Hub gene expression in LUAD is increased, and its increased expression is related to poor prognosis of LUAD patients. Finally, the expression of SKA1/2/3 and its correlation with clinicopathological features were verified in 30 clinical LUAD samples.

Conclusions: SKA1/2/3 may serve as a potential prognostic biomarker and target for LUAD. In addition, SKA 1/2/3 may affect the prognosis of LUAD through DNA replication, cell cycle, homologous recombination and p53 signaling pathway.
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http://dx.doi.org/10.21037/tlcr.2020.01.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225159PMC
April 2020

Results of video-assisted thoracic surgery versus thoracotomy in surgical resection of pN2 non-small cell lung cancer in a Chinese high-volume Center.

Surg Endosc 2020 May 11. Epub 2020 May 11.

Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.

Purpose: To investigate the short-term outcomes and long-term oncological efficacy of video-assisted thoracic surgery (VATS) for surgical treatment of pN2 non-small cell lung cancer (NSCLC) compared with open thoracotomy (OT).

Patients And Methods: We retrospectively collected data from 1034 patients who underwent pulmonary resection and systemic lymph node dissection for pathological N2 NSCLC from September 2005 to December 2017 (536 patients in VATS group and 498 patients in OT group). Propensity score matching was applied to reduce the confounding effects. Factors affecting survival were assessed by Kaplan-Meier estimates and Cox regression analysis.

Results: The VATS procedure was associated with shorter operative time compared with the OT procedure (147.96 ± 58.91 min vs. 165.34 ± 58.91 min, P < 0.001). No significant difference was identified between the two groups in the number of dissected mediastinal lymph nodes (MLNs) and number of dissected MLNs stations. More patients after VATS procedure received postoperative adjuvant therapy (83.4% vs. 75.5%, P = 0.002). At a median follow-up of 36 (range 4-150) months, comparing VATS procedure and OT procedure, no significant differences were noted in 5-year DFS (20.7% vs. 22.5%, P = 0.89) and 5-year OS (30.7% vs. 34.5%, P = 0.821). The VATS procedure was not found to be an independent predictor of DFS (hazard ratio, 0.986; 95% CI, 0.809 to 1.202) or OS (hazard ratio, 0.977; 95% CI 0.802 to 1.191).

Conclusion: In this large propensity-matched comparison, the VATS procedure offered comparable short-term outcomes and long-term oncological efficacy for patients with pN2 NSCLC when compared with OT procedure.
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http://dx.doi.org/10.1007/s00464-020-07624-2DOI Listing
May 2020