Publications by authors named "Sukki Cho"

119 Publications

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2021 Feb 24:1-9. Epub 2021 Feb 24.

Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.

Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.

Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.

Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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http://dx.doi.org/10.1159/000514131DOI Listing
February 2021

Prognostic significance of tumor spread through air spaces in patients with stage IA part-solid lung adenocarcinoma after sublobar resection.

Lung Cancer 2021 02 5;152:21-26. Epub 2020 Dec 5.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives: The purpose of this study was to assess the clinicopathologic implications of tumor spread through air spaces (STAS) in patients with stage IA part-solid lung adenocarcinoma after sublobar resection.

Materials And Methods: Medical records of patients with stage IA part-solid adenocarcinoma who underwent curative pulmonary resection between February 2009 and December 2016 were retrospectively reviewed. The clinicopathological features of STAS and its influence on postoperative recurrence and survival were investigated.

Results: Among the 115 patients with stage IA part-solid adenocarcinoma who underwent wedge resection, 20 (17.4 %) had STAS. The multivariable analysis showed presence of STAS [HR (hazard ratio), 9.447; p = 0.002) and a larger invasive component size (HR, 1.097; p = 0.034) were independent risk factors for recurrence. The 5-year freedom from recurrence rates were 62.4 % and 97.9 % in cases with and without STAS, respectively (p < 0.001), and the 5-year disease-free survival rates were 58.5 % and 97.9 % in cases with and without STAS, respectively (p < 0.001). The presence of STAS was associated with old age (p = 0.030), male gender (p = 0.023), acinar predominant histologic pattern (p = 0.004), presence of micropapillary pattern (p < 0.001), lymphovascular invasion (p < 0.001) and larger invasive component (p < 0.001).

Conclusion: STAS could be an important prognostic factor in patients with stage IA part-solid lung adenocarcinoma after sublobar resection. Effective preoperative evaluation and postoperative surveillance may help improve the outcome of patients with small part-solid nodules, particularly when accompanied by STAS.
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http://dx.doi.org/10.1016/j.lungcan.2020.12.001DOI Listing
February 2021

Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer.

Mod Pathol 2021 03 16;34(3):549-561. Epub 2020 Nov 16.

Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I: <2500 μm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 μm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage. In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p < 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection.
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http://dx.doi.org/10.1038/s41379-020-00709-2DOI Listing
March 2021

The differential prognostic impact of spread through air spaces in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor.

J Thorac Cardiovasc Surg 2020 Oct 7. Epub 2020 Oct 7.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: We evaluated the differential prognostic impact of spread through air spaces (STAS) in early-stage lung adenocarcinoma after lobectomy according to the pT descriptor.

Methods: The study population included 506 patients who underwent lobectomy with mediastinal lymph node dissection for pT1b, pT1c, and pT2a adenocarcinoma between 2011 and 2016. We divided the study population into 2 groups according to STAS status, ie, STAS (+) versus STAS (-), and stratified them according to the pT descriptor. A Cox proportional hazard model and inverse probability of treatment weight-adjusted Kaplan-Meier curves were used to evaluate the prognostic impact of STAS on recurrence-free survival (RFS) and its independency in each stratum.

Results: Multivariable Cox proportional hazard regression analysis demonstrated that in pT1b and pT1c strata, STAS (+) patients had a 7.02-fold and 2.89-fold greater risk of recurrence than STAS (-) patients, respectively. However, in the pT2a stratum, STAS did not affect RFS. And the RFS of the STAS (+) pT1b/c strata was similar to that of the pT2a stratum. In the pT1b/c strata, inverse probability of treatment weighting-adjusted Kaplan-Meier curves also showed that RFS was significantly worse when STAS was present. Furthermore, the risks for locoregional and distant recurrence were both greater when STAS was present.

Conclusions: The presence of STAS increased the risk of recurrence independently from other poor prognostic factors in patients with pT1b/cN0M0 adenocarcinoma who underwent lobectomy, but not in pT2a patients. The presence of STAS in pT1b/cN0M0 adenocarcinoma was associated with a similar risk of recurrence to that of pT2aN0M0 adenocarcinoma.
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http://dx.doi.org/10.1016/j.jtcvs.2020.09.098DOI Listing
October 2020

Comparison of survival outcomes between sublobar resection and lobectomies in early-stage lung adenocarcinoma by propensity score matching analysis.

Indian J Thorac Cardiovasc Surg 2020 Jul 3;36(4):382-387. Epub 2020 Mar 3.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi South Korea.

Background: The aim of this study was to investigate the clinical outcomes of sublobar resections and compare these with those of lobectomies in early-stage lung adenocarcinoma patients.

Methods: We retrospectively reviewed medical records of 871 patients who underwent lobectomies or sublobar resections for early-stage lung adenocarcinomas. Two hundred thirty-five (27.0%) patients underwent sublobar resections (wedge and segmentectomies), and 636 (73.0%) underwent lobectomies. Propensity score matching resulted in 2 groups each with 219 patients. Survival analysis was performed.

Results: Mean age of matched patients was 61.9 (± 10.38, range of 21 to 91) years, mean follow-up period was 50.8 (± 27.57, range of 6.1 to 128.9) months, and mean tumor size was 15.2 (± 6.49, range of 3.0 to 45.0) mm. Overall recurrence rate was 9.4% (41 patients), and it was 8.7% (19 patients) in sublobar resection patients and 9.6% (21 patients) in lobectomy patients. Rates and sites of recurrence were not significantly different between the two surgical groups ( = 0.500 and 0.401, respectively). Overall 5-year survival and recurrence-free survival of sublobar resection patients were 90.6 and 89.5%, respectively, whereas those of lobectomy patients were 91.9 and 88.3%, respectively. No significant differences in overall 5-year survival rate or recurrence-free survival rate were found between the two groups ( = 0.636 and = 0.975, respectively).

Conclusions: Prognosis of early-stage lung adenocarcinoma treated with sublobar resection was not inferior to that treated with lobectomy in carefully selected cases. Further investigations, including randomized controlled trials, are needed to identify the equivalent oncologic efficacy of sublobar resections.
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http://dx.doi.org/10.1007/s12055-019-00897-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525899PMC
July 2020

Fistulas between the Esophagus and Adjacent Vital Organs in Esophageal Cancer.

Authors:
Sukki Cho

Korean J Thorac Cardiovasc Surg 2020 Aug;53(4):211-216

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Esophageal fistulas may occur in an advanced stage or as a potentially life-threatening complication of treatment. They can be divided into esophageal-respiratory and esophageal-aorta fistulas. The diagnosis is confirmed with fluoroscopy using dilute barium oral contrast, followed by thin-section computed tomography, which defines the precise location and extent of the fistula. Flexible esophagoscopy and bronchoscopy are required for confirmation and anatomic assessment of the suspected fistula and provide additional information for treatment planning. Contamination is traditionally controlled by surgical exclusion, along with a jejunal feeding tube. Currently, fully covered self-expanding metal stents are the primary treatment option.
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http://dx.doi.org/10.5090/kjtcs.2020.53.4.211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409885PMC
August 2020

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2020 13;98(12):897-904. Epub 2020 Aug 13.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).

Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed.

Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively).

Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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http://dx.doi.org/10.1159/000509658DOI Listing
December 2020

Predictive Factors for Lymph Node Metastasis in Clinical Stage I Part-Solid Lung Adenocarcinoma.

Ann Thorac Surg 2021 02 9;111(2):456-462. Epub 2020 Jul 9.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea; Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Accurate clinical staging of tumors with a small solid portion is essential for developing an appropriate treatment plan. This study evaluated predictive factors for lymph node (LN) metastasis in patients with clinical stage I part-solid lung adenocarcinoma.

Methods: Medical records of patients with clinical stage I part-solid adenocarcinoma who underwent anatomic pulmonary resection with systematic node evaluation between January 2009 and June 2018 were retrospectively reviewed. To identify predictive factors for LN metastasis, univariate and multivariable logistic regression analyses were performed.

Results: Among the 593 patients in this study, the overall prevalence of LN metastasis was 3.7% (n = 22), which included 3.0% (n = 18) of patients with N1 LN metastasis and 1.5% (n = 9) of patients with N2 LN metastasis. Combined N1 and N2 nodal involvement was observed in 5 patients. Nodal metastasis was not observed in tumors with a solid portion sized 1.1 cm or smaller. The nodal metastasis rates in cT1b, cT1c, and cT2a tumors were 5.5% (13 of 237), 7.1% (6 of 84), and 13.6% (3 of 22), respectively. According to the multivariable analysis, predictive factors included the size of the solid portion (P = .015) and the high maximum standardized uptake value (SUVmax) of the primary tumor (P = .044).

Conclusions: Large solid portion and high SUVmax of the primary tumor were predictive factors of LN metastasis in patients with clinical stage I part-solid lung adenocarcinoma. Systematic LN evaluation should be performed, especially in those who have a large solid portion and high SUVmax of the primary tumor.
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http://dx.doi.org/10.1016/j.athoracsur.2020.05.083DOI Listing
February 2021

Correction to: Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

Ann Surg Oncol 2020 Dec;27(Suppl 3):981-982

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

In the original article there are errors in Fig. 3. Following is the corrected figure.
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http://dx.doi.org/10.1245/s10434-020-08840-9DOI Listing
December 2020

Genetic Alterations in Preinvasive Lung Synchronous Lesions.

Cancer Res Treat 2020 Oct 5;52(4):1120-1134. Epub 2020 Jun 5.

Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD).

Materials And Methods: We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing.

Results: Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions.

Conclusion: Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.
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http://dx.doi.org/10.4143/crt.2020.307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577825PMC
October 2020

Impact of idiopathic pulmonary fibrosis on recurrence after surgical treatment for stage I-III non-small cell lung cancer.

PLoS One 2020 29;15(6):e0235126. Epub 2020 Jun 29.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

Background: Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, its effect on recurrence after curative surgery remains unclear.

Objectives: This study aimed to determine the impact of IPF on recurrence-free survival following curative surgical resection of stage I-III non-small cell lung cancer (NSCLC) and investigate the effects of patient and surgical factors on the risk of recurrence.

Methods: We reviewed retrospectively collected data of patients with surgically resected stage I-III NSCLC from two tertiary care hospitals in South Korea. By propensity score matching, patients with IPF (LC with IPF) were matched to those without IPF (LC without IPF).

Results: In total, 3416 patients underwent surgical resection, and 96 were diagnosed with underlying IPF. In the LC with IPF group, 89.6% patients were men, and the average age was 69.7 years. Sublobar resection was performed more frequently in the LC with IPF group than in the LC without IPF group, while the rate of mediastinal lymph node dissection and dissected node number were lower in the former group. The 5-year recurrence-free survival rate was significantly lower in the LC with IPF group (49.2%) than in the LC without IPF group (69.1%; P<0.001). Multivariable Cox regression analysis revealed that IPF and postoperative stage III were independent risk factors for recurrence.

Conclusions: IPF may increase the risk of recurrence after curative surgical treatment for NSCLC. Close surveillance for recurrence is mandatory for patients with underlying IPF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235126PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323957PMC
September 2020

Differentiating thymoma from thymic cyst in anterior mediastinal abnormalities smaller than 3 cm.

J Thorac Dis 2020 Apr;12(4):1357-1365

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.

Background: Computed tomography (CT) screening for lung cancer has led to frequent findings of small anterior mediastinal masses. It is very hard to distinguish small thymomas from thymic cysts. The objective of this study was to develop a clinical model for predicting small thymomas (<3 cm) in asymptomatic patients.

Methods: Patients who underwent thymectomy for anterior mediastinal masses between 2004 and 2016 were included. All preoperative CT scans (pre- and post-enhanced) were retrospectively reviewed. Size, location, contour, shape, presence of calcification, and enhancement [Hounsfield units (HU)] were evaluated. A nomogram was built based on the predictive factors. For external validation, patients undergoing thymectomy in 2017 were enrolled and thymoma prediction was computed using the proposed nomogram.

Results: The study population consisted of 43 patients with thymoma and 57 with thymic cyst. The multivariable analysis identified a lobulated contour and a large difference in HU between post- and pre-enhancement as predictive factors of thymoma. These factors were included in the nomogram, which showed 95% (19/20) power for predicting thymoma after external validation.

Conclusions: This clinical model can be used to predict thymoma in patients with small, asymptomatic thymic abnormalities on CT screening.
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http://dx.doi.org/10.21037/jtd.2020.02.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212157PMC
April 2020

Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces.

Ann Surg Oncol 2020 Oct 3;27(11):4394-4403. Epub 2020 May 3.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

Objectives: Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA.

Materials And Methods: Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated.

Results: The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk.

Conclusions: The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.
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http://dx.doi.org/10.1245/s10434-020-08508-4DOI Listing
October 2020

Conversion surgery after cetuximab or bevacizumab plus FOLFIRI chemotherapy in colorectal cancer patients with liver- and/or lung-limited metastases.

J Cancer Res Clin Oncol 2020 Sep 1;146(9):2399-2410. Epub 2020 May 1.

Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro-173-beon-gil, Seongnam, 13620, Republic of Korea.

Purpose: Some metastatic colorectal cancer (mCRC) patients receive conversion surgery (CS), including metastasectomy after palliative chemotherapy. Although targeted agents significantly improved the outcomes, the clinical outcome of CS in the targeted agent era has not yet been thoroughly investigated.

Methods: We analyzed the clinical data of 96 mCRC patients who initially had unresectable liver- and/or lung-limited metastases and underwent first-line cetuximab or bevacizumab plus FOLFIRI between January 2013 and June 2017.

Results: Liver-limited metastasis was seen in 44 patients (45.8%), lung-limited metastases in 21 patients (21.9%), and both liver and lung metastases in 31 patients (32.3%). Among them, 37 patients (38.5%) received cetuximab, and 59 patients (61.5%) received bevacizumab plus FOLFIRI. Overall response rate was 63.9% and 40.7%, respectively (p = 0.035). After median 8.7 (range 2.5-27.3) months, CS was performed in 11 patients (29.7%) in cetuximab group and 15 patients (25.4%) in bevacizumab group (p = 0.646). Median overall survival has not been reached in R0-resected patients (n = 23), during the median follow-up period of 22.5 (range 9.8-54.5) months. Median disease-free survival was 7.1 (95% CI 2.5-11.7) months: 11.0 (95% CI 3.1-19.0) months in cetuximab group and 3.2 (95% CI 0.0-7.8) months in bevacizumab group (p = 0.422). There was no progression after 18.5 months and disease-free survival reached a plateau at 19.9%.

Conclusions: A substantial proportion of patients could receive CS after cetuximab or bevacizumab plus FOLFIRI chemotherapy. R0-resected patients had excellent overall survival, although 80.1% of them eventually experienced recurrence. Some patients could achieve durable disease-free state.
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http://dx.doi.org/10.1007/s00432-020-03233-7DOI Listing
September 2020

ASO Author Reflections: Understanding Subsolid Lung Adenocarcinoma with Cystic Airspaces (LACA).

Ann Surg Oncol 2020 Oct 30;27(11):4404. Epub 2020 Apr 30.

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

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http://dx.doi.org/10.1245/s10434-020-08528-0DOI Listing
October 2020

Prognostic stratification of pathological node-negative lung adenocarcinoma by carcinoembryonic antigen level.

Interact Cardiovasc Thorac Surg 2020 06;30(6):820-826

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.

Objectives: Carcinoembryonic antigen (CEA) is a well-known tumour marker for lung adenocarcinoma (AC). This study was conducted to evaluate the clinical characteristics and prognosis of patients with pathological node-negative lung AC who have a high preoperative level of CEA.

Methods: Among 2124 patients with lung AC between 2003 and 2016, 858 patients were enrolled. CEA levels were dichotomized as normal (≤5 ng/ml) or high (>5 ng/ml). According to the levels of CEA between 6 and 12 months after surgery, patients were divided into a normalized and a remained-high group. Propensity score matching was used to compare 80 patients without adjuvant chemotherapy (ACT) with 39 patients with ACT. Kaplan-Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis were performed for recurrence-free survival (RFS) and overall survival (OS).

Results: The multivariable analysis showed that high maximum standardized uptake value and T2 stage were more common in patients with high levels of CEA. The median follow-up period was 52.8 months (range 6-169 months). The 5-year RFS and OS rates were 89.3% and 68.9% and 92.8% and 77.2% in normal patients and patients with high levels of CEA, respectively, with a statistically significant difference. The 5-year RFS was 79.4% and 39.2% in the normalized and remained-high groups after surgery, respectively (P = 0.011). The 5-year RFS and OS rates were 68.9% and 62.2% and 80.1% and 82.9% in patients without and with ACT, respectively. After propensity score matching, RFS was not significantly different between patients without and with ACT (P = 0.500); however, OS was significantly better in patients with ACT than in those without ACT (P = 0.001).

Conclusions: The clinicopathological characteristics, RFS and OS of patients with lung AC might be well discriminated by preoperative CEA levels. In patients with node-negative disease and high CEA levels, those with normalized CEA levels had a significantly better prognosis than those with persistently high CEA levels.
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http://dx.doi.org/10.1093/icvts/ivaa035DOI Listing
June 2020

Risk factors for primary lung cancer among never-smoking women in South Korea: a retrospective nationwide population-based cohort study.

Korean J Intern Med 2020 05 19;35(3):692-702. Epub 2020 Feb 19.

Department of Occupational and Environmental Medicine, Seoul St. Mary's Hospital, of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females.

Methods: The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as "newly diagnosed lung cancer".

Results: After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence.

Conclusion: Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.
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http://dx.doi.org/10.3904/kjim.2019.283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214358PMC
May 2020

Do ground-glass opacity-dominant features have prognostic significance in node-negative adenocarcinomas with invasive components of similar sizes?

Eur J Cardiothorac Surg 2020 06;57(6):1189-1194

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objectives: The purpose of this study was to analyse the prognostic significance of the dominant features of ground-glass opacities (GGOs) in part-solid node-negative adenocarcinomas with invasive components of similar sizes.

Methods: From 2004 to 2017, a total of 544 patients with a diagnosis of part-solid pathological node-negative adenocarcinoma with an invasive component <20 mm in size were selected. The enrolled patients were categorized into 2 groups: a GGO-dominant [50% < GGO (%) < 100%, n = 245] group (group 1) and a solid-dominant [0% < GGO (%) ≤ 50%, n = 299] group (group 2). To analyse the prognostic significance of GGO-dominant features, propensity score matching incorporating variables such as age, sex, preoperative pulmonary function, operation methods and size of the solid component was performed.

Results: Propensity score matching produced 92 patients in each group for the prognostic analysis. The mean size of the solid part was 8.8 mm in the GGO-dominant group and 9.0 mm in the solid-dominant group (P = 0.34); the mean size of the total lesion was 22.2 mm in the GGO-dominant group and 14.9 mm in the solid-dominant group (P < 0.001). The 5-year overall survival rates were 96.7% in group 1 and 96.2% in group 2 (P = 0.52), and the 5-year disease-free survival rates were 96.7% in group 1 and 94.3% in group 2 (P = 0.48).

Conclusions: Although the total sizes of the GGO-dominant lesions were larger than those of the solid-dominant lesions, the prognosis of patients with GGO-dominant lesions was not significantly different from that of patients with solid-dominant lesions in node-negative adenocarcinomas with a similar invasive component size <20 mm.
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http://dx.doi.org/10.1093/ejcts/ezaa016DOI Listing
June 2020

Endoscopic Vacuum Therapy in the Management of Postoperative Leakage After Esophagectomy.

World J Surg 2020 01;44(1):179-185

Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Background: Postoperative leakage after esophagectomy is associated with significant life-threatening complications. Recently, endoscopic vacuum therapy (EVT) was introduced and has been successfully used as a new treatment option. The purpose of this study was to evaluate the safety and efficacy of EVT for the management of postoperative leakage after esophagectomy.

Methods: A total of 22 patients were treated with either intraluminal or intracavitary EVT for the management of postoperative leakage from May 2012 to April 2018. The location of leakage was intrathoracic in 17 patients and cervical in five patients. The outcomes of EVT were analyzed retrospectively.

Results: Complete postoperative leakage closure was achieved in 19 of 22 patients. The median duration of EVT application was 14 days (range 2-103), and a median number of three EVT systems (range 1-14) were used. In 19 patients who were successfully managed with EVT, oral feeding was possible a median of 15 days after the first day of treatment. There were no cases of mortality related to postoperative leakage.

Conclusions: EVT is a well-tolerated and effective therapeutic option for the treatment of various types of postoperative leakage after esophagectomy.
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http://dx.doi.org/10.1007/s00268-019-05228-zDOI Listing
January 2020

Surgical treatment of pulmonary oligorecurrence after curative resection for non-small-cell lung cancer.

Interact Cardiovasc Thorac Surg 2020 01;30(1):18-23

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul, Korea.

Objectives: The most appropriate therapeutic strategy for patients with pulmonary oligorecurrence after curative resection of non-small-cell lung cancer (NSCLC) is unclear; therefore, characterizing the results of various treatments for pulmonary oligorecurrence would be valuable. This study compared the prognosis of operative and non-operative treatment for pulmonary oligorecurrence after complete resection of NSCLC.

Methods: Among 2230 patients from a prospective lung cancer database who underwent surgical resection between 2004 and 2014, 486 patients (22%) experienced recurrence, including 254 with pulmonary recurrence and 102 with pulmonary oligorecurrence (5 or fewer metastatic lesions). Post-recurrence survival (PRS) rates were compared between those who received operative or non-operative treatment, including chemotherapy, radiotherapy, chemoradiotherapy and best supportive care.

Results: Among 102 patients with pulmonary oligorecurrence, 41 patients received operative treatment and 61 received non-operative treatment (34 chemotherapy, 15 radiotherapy, 9 chemoradiotherapy and 3 best supportive care). The patients who received operative treatment were significantly younger at the first operation than those in the non-operative group and had better performance status, lower pathological T stage at the first operation, younger age at recurrence and fewer metastatic lesions. The median PRS was 46.4 months, and the 5-year PRS rates were 67% and 26% in the operative and non-operative groups, respectively. The multivariable analysis revealed that undergoing video-assisted thoracoscopic surgery at the first operation and receiving operative treatment for recurrence were independent prognostic factors for more favourable PRS.

Conclusions: Operative treatment of pulmonary oligorecurrence after curative resection significantly prolonged the PRS in patients who underwent curative resection for NSCLC.
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http://dx.doi.org/10.1093/icvts/ivz221DOI Listing
January 2020

Risk factors for postoperative complications and long-term survival in lung cancer patients older than 80 years.

J Thorac Dis 2019 Jun;11(6):2226-2228

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

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http://dx.doi.org/10.21037/jtd.2019.05.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626789PMC
June 2019

Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

Ann Surg Oncol 2019 Oct 16;26(11):3756-3764. Epub 2019 Jul 16.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC.

Methods: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated.

Results: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P = 0.02) in tumor tissues.

Conclusions: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.
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http://dx.doi.org/10.1245/s10434-019-07614-2DOI Listing
October 2019

Perioperative change in neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in patients with completely resected primary pulmonary sarcomatoid carcinoma.

J Thorac Dis 2019 Mar;11(3):819-826

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.

Background: There has been controversy regarding prognostic factors for surgically resected primary pulmonary sarcomatoid carcinoma (PSC). Recently, several studies have shown that neutrophil-to-lymphocyte ratio (NLR) was a prognostic factor for various types of cancers from multiple organs. Therefore, we performed this study to evaluate whether NLR is related to prognosis after complete surgical resection of primary PSC.

Methods: From Oct. 2003 to Sep. 2015, a total of 50 patients underwent surgical resection for primary PSC. After excluding patients with any history of other malignancy and incompletely resected cases, a total of 37 patients were included, and data were retrospectively collected and analyzed. Change in postoperative NLR and the initial NLR (ΔNLR) was calculated from the perioperative complete blood count (CBC) results.

Results: Mean age of the cohort was 62.2±1.9 years, and 31 patients (83.8%) were male. Twenty patients (54.1%) were revealed as pN0. Overall 5-year survival rate was 50.3%. Seventeen patients (45.9%) had locoregional or distant metastases. Univariate survival analysis revealed age >70, ΔNLR >17 as risk factors for overall survival (P=0.009, 0.005) and disease-free survival (P=0.036, 0.018). Multivariate Cox-regression analysis revealed age >70 and ΔNLR >17 as independent risk factors for overall survival and ΔNLR >17 as the only independent risk factor for the disease-free survival.

Conclusions: In patients with completely resected primary PSC, perioperative ΔNLR had a significant effect on the overall survival and disease-free survival. Older age was also an independent risk factor for overall survival.
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http://dx.doi.org/10.21037/jtd.2019.02.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462731PMC
March 2019

Glucose transporter 3 gene variant is associated with survival outcome of patients with non-small cell lung cancer after surgical resection.

Gene 2019 Jun 4;703:58-64. Epub 2019 Apr 4.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04-2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18-2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15-5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.
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http://dx.doi.org/10.1016/j.gene.2019.04.013DOI Listing
June 2019

Clinical Significance of Pleural Attachment and Indentation of Subsolid Nodule Lung Cancer.

Cancer Res Treat 2019 Oct 25;51(4):1540-1548. Epub 2019 Mar 25.

Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Respiratory Center, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival.

Materials And Methods: Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed.

Results: Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91).

Conclusion: Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.
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http://dx.doi.org/10.4143/crt.2019.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790827PMC
October 2019

To do or not to do lymphadenectomy in part-solid lung adenocarcinoma.

J Thorac Dis 2018 Nov;10(Suppl 33):S3899-S3901

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.

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http://dx.doi.org/10.21037/jtd.2018.09.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297456PMC
November 2018

Cuff Technique for Small-Diameter Vascular Grafts in the Systemic Arterial Circulation of the Rat.

Korean J Thorac Cardiovasc Surg 2018 Dec 5;51(6):423-426. Epub 2018 Dec 5.

Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine.

This study determined the feasibility of the cuff technique for small-caliber vascular grafts in a rat model. A graft was implanted with the cuff technique or suture technique in a 1-cm segment of the abdominal aorta in 12 rats. The mean aortic clamp time was 29 minutes with the cuff technique and 44 minutes with the suture technique; the cuff technique was significantly shorter. Abdominal angiography at 1 week after implantation showed no significant stenosis in 9 rats, focal stenosis of the mid-portion of the graft in 1 rat with each technique, and total occlusion of the graft in 1 rat with the suture technique. We have successfully used the cuff technique for anastomosis for small-caliber vascular grafts in an animal model.
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http://dx.doi.org/10.5090/kjtcs.2018.51.6.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301317PMC
December 2018

TSC2 genetic variant and prognosis in non-small cell lung cancer after curative surgery.

Thorac Cancer 2019 02 26;10(2):335-340. Epub 2018 Dec 26.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

This study was conducted to investigate the associations between polymorphisms of genes involved in the LKB1 pathway and the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Twenty-three single nucleotide polymorphisms (SNPs) in the LKB1 pathway were investigated in 782 patients with NSCLC who underwent curative surgery. The association of SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. Among the 23 SNPs investigated, TSC2 rs30259G > A was associated with significantly worse OS and DFS (adjusted hazard ratio for OS 1.88, 95% confidence interval 1.21-2.91, P = 0.005; adjusted hazard ratio for DFS 1.65, 95% confidence interval 1.15-2.38, P = 0.01, under codominant models, respectively). Subgroup analysis showed that SNPs were significantly associated with survival outcomes in squamous cell carcinoma, ever-smokers, and stage I, but not in adenocarcinoma, never-smokers, and stage II-IIIA. The results suggest that TSC2 rs30259G > A may be useful to predict prognosis in patients with NSCLC, especially squamous cell carcinoma, after curative surgery.
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http://dx.doi.org/10.1111/1759-7714.12951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360237PMC
February 2019

Quiescin Sulfhydryl Oxidase 1 (QSOX1) Secreted by Lung Cancer Cells Promotes Cancer Metastasis.

Int J Mol Sci 2018 Oct 17;19(10). Epub 2018 Oct 17.

Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.

As lung cancer shows the highest mortality in cancer-related death, serum biomarkers are demanded for lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS⁻MS proteomic analysis. Quiescin sulfhydryl oxidase (QSOX1) was selected as a biomarker candidate from the enriched proteins in the secretion of lung cancer cells. QSOX1 levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients ( < 0.05, Area Under curve (AUC) = 0.89) when measured by multiple reaction monitoring (MRM). Higher levels of QSOX1 were also uniquely detected in lung cancer tissues, among several other solid cancers, by immunohistochemistry. QSOX1-knock-downed Lewis lung cancer (LLC) cells were less viable from oxidative stress and reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and be involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.
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http://dx.doi.org/10.3390/ijms19103213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214099PMC
October 2018