Publications by authors named "Hailei Du"

14 Publications

  • Page 1 of 1

Development and validation of an autophagy-related prognostic signature in esophageal cancer.

Ann Transl Med 2021 Feb;9(4):317

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Autophagy has a dual function in cancer, and its role in carcinogenesis of the esophagus remains poorly understood. In the present study, we explored the prognostic value of autophagy in esophageal cancer (ESCA), one of the leading causes of cancer-related deaths worldwide.

Methods: Using ESCA RNA-sequencing (RNA-Seq) data from 158 primary patients with ESCA, including esophageal adenocarcinoma and esophageal squamous cell carcinoma, were downloaded from The Cancer Genome Atlas (TCGA) for this study. We obtained differentially expressed autophagy-related genes (ARGs) by the "limma" package of R. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses unveiled several fundamental signaling pathways associated with the differentially expressed ARGs in ESCA. Univariate Cox regression analyses were used to estimate associations between ARGs and overall survival (OS) in the TCGA ESCA cohort. A Cox proportional hazards model (iteration =1,000) with a lasso penalty was used to create the optimal multiple-gene prognostic signature utilizing an R package called "glmnet".

Results: A prognostic signature was constructed with four ARGs (, , and ) in the training set, which significantly divided ESCA patients into high- and low-risk groups in terms of OS [hazard ratio (HR) =1.508, 95% confidence interval (CI): 1.201-1.894, P<0.001]. In the testing set, the risk score remained an independent prognostic factor in the multivariate analyses (HR =1.572, 95% CI: 1.096-2.257, P=0.014). The area under the curve (AUC) of the receiver operating characteristic (ROC) predicting 1-year survival showed a better predictive power for the prediction model. The AUC in training and testing cohorts were 0.746 and 0.691, respectively. Therefore, the prognostic signature of the four ARGs was successfully validated in the independent cohort.

Conclusions: The prognostic signature may be an independent predictor of survival for ESCA patients. The prognostic nomogram may improve the prediction of individualized outcome. This study also highlights the importance of autophagy in the outcomes of patients with ESCA.
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http://dx.doi.org/10.21037/atm-20-4541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944288PMC
February 2021

The Prognostic Value of Tumor Mutation Burden and Immune Cell Infiltration in Thymic Epithelial Tumors.

Ann Clin Lab Sci 2021 Jan;51(1):44-54

Department of Thoracic Surgery, Ruijin Hospital; Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objective: The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs).

Methods: We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package.

Results: Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (<0.05), and higher Masaoka stages (<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs.

Conclusion: The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.
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January 2021

Beclin-1 expression is associated with prognosis in a Bcl-2-dependent manner in non-small cell lung cancer.

Oncol Lett 2020 Oct 15;20(4). Epub 2020 Jul 15.

Department of Respiratory and Critical Care Medicine, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 201821, P.R. China.

Beclin-1 and Bcl-2 expression abnormalities have been confirmed in different types of cancer. As important regulators of autophagy and apoptosis, respectively, these molecules serve a complex role in tumorigenesis. However, limited information is currently available regarding the association between Beclin-1 and Bcl-2 in (NSCLC). In the present study, the expression levels of Beclin-1 and Bcl-2 were detected in lung cancer tissues, and their prognostic significance was analyzed for NSCLC. A total of 120 patients with lung cancer who underwent surgical resection were included in the present study. Beclin-1 and Bcl-2 expression was assessed using immunohistochemistry and their associations with the overall survival (OS) in patients with NSCLC was examined. The expression rate of Beclin-1 was significantly lower in NSCLC tissues compared with that in adjacent tissues, whereas the expression rate of Bcl-2 was significantly higher in lung cancer tissues compared with that in adjacent tissues. Additionally, Beclin-1 and Bcl-2 protein expression was strongly associated (P<0.05) in NSCLC. Patients with NSCLC with low Beclin-1 expression were in more advanced stages, with more lymph node metastasis and more poorly differentiated tumors. Similarly, patients with NSCLC with high Bcl-2 expression were also in a more advanced stage and had more lymph node metastasis. Cox regression analysis revealed that the association between Bcl-2 expression and survival was not significant, while a multivariate analysis revealed that Beclin-1 expression was significantly associated with OS. Notably, Beclin-1 expression was significantly associated with OS only in patients with high Bcl-2 expression. In conclusion, the present data indicated that the autophagy activity is decreased in NSCLC. Beclin-1 expression was downregulated, while Bcl-2 expression was upregulated in NSCLC tissues compared with that in adjacent tissues. Additionally, these two proteins were associated with the occurrence and progression of NSCLC. Beclin-1 may be a promising prognostic marker for patients with NSCLC with high Bcl-2 expression. The present findings provided a more accurate prognostic assessment for patients with NSCLC. Furthermore, they may be used to actively follow-up and promptly treat patients with a poor prognosis, which may benefit a greater number of patients with NSCLC.
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http://dx.doi.org/10.3892/ol.2020.11870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413043PMC
October 2020

Double lung transplantation for Sjögren's syndrome-related interstitial lung disease: a case report and review of literature.

Ann Transl Med 2020 Jul;8(14):888

Department of Thoracic Surgery, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

In this study, we present a case of 65-year-old male patient with suspected Sjögren's syndrome-related interstitial lung disease (SS-ILD) with initial symptoms of limb edema and acute respiratory failure. He was treated with immunosuppressor, respiratory support, dialysis, immunomodulatory, and anti-inflammatory medications. However, no significant response was shown to anti-fibrotic treatments and his respiratory function deteriorated. Double lung transplantation was thus indicated considering the irreversible interstitial changes in both lungs. The surgical procedure was complicated, and the role of enhanced recovery after surgery (ERAS) for this critical patient was discussed. The patient experienced hemorrhage, pulmonary infection, and peripheral neuropathy after surgery, but he was cured by the multidisciplinary team. He had a satisfactory quality of life at 1-year follow-up. This case report describes the details of double lung transplantation in a patient with advanced SS-ILD. Important considerations include the indications for and timing of transplantation, the effects of long-term immunosuppression on wound healing, and extrapulmonary organ dysfunction. Based on a review of the published literature and a consideration of the short-term outcomes, lung transplantation for this individual with an autoimmune disease appears to be safe and feasible. SS-ILD should not be a contraindication to transplantation; however, patients with advanced pulmonary involvement should be carefully selected after a multidisciplinary evaluation. More long-term follow-up and further comparative studies are needed in the future.
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http://dx.doi.org/10.21037/atm-20-3516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396791PMC
July 2020

Methods for Dissecting Intersegmental Planes in Segmentectomy: A Randomized Controlled Trial.

Ann Thorac Surg 2020 07 12;110(1):258-264. Epub 2020 Mar 12.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai. Electronic address:

Background: The perioperative outcomes of the use of stapling devices versus electrocautery to dissect intersegmental planes in patients undergoing segmentectomy for small pulmonary lesions is still unclear. The aim of this randomized controlled trial was to compare the perioperative outcomes of these two methods.

Methods: A single-center, prospective, participant-blinded, randomized controlled trial (NCT03192904) was conducted with a preplanned sample size of 136. The primary outcome was the incidence of postoperative complications. Secondary outcomes included duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stay, loss of lung function, and medical costs.

Results: The trial was stopped early as a result of a marked difference in the primary outcome between groups at a scheduled interim check of the data after recruiting 70 patients. The incidence of postoperative complications (eg, air leakage) was higher in the electrocautery group than in the stapler device group (11/32, 34.4% vs 2/33, 6.1%, P = .004). There were no differences in duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stays, loss of lung function, or total medical cost, although the per-patient cost of medical materials was higher in the stapler device group (US$4214.6 ± 1185.4 vs $3260.1 ± 852.6, P < .001).

Conclusions: Among patients undergoing segmentectomy, the use of stapler devices to divide intersegmental planes decreased postoperative complications without further compromising lung function or increasing economic burden.
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http://dx.doi.org/10.1016/j.athoracsur.2020.02.013DOI Listing
July 2020

Endoscope-assisted mediastinal drainage therapy for anastomosis leakage after esophagectomy: a retrospective cohort study.

Ann Transl Med 2019 Dec;7(23):747

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy.

Methods: Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed.

Results: Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P<0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P<0.001).

Conclusions: Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH.
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http://dx.doi.org/10.21037/atm.2019.11.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989978PMC
December 2019

Comparison of video-assisted thoracic surgery with open surgery in the treatment of ectopic mediastinal parathyroid tumors.

J Thorac Dis 2017 Dec;9(12):5171-5175

Department of thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Background: To investigate the therapeutic effect of different surgical treatment for ectopic mediastinal parathyroid tumors and pathological features.

Methods: A total of 21 patients who were diagnosed with ectopic mediastinal parathyroid tumors and underwent surgeries in our department from May 1995 to May 2015 were collected and retrospectively analyzed.

Results: Twenty-one patients including 8 female (36.4%) and 13 male (63.6%) were collected. Among these patients, 9 cases were treated with video-assisted thoracic surgery (VATS), while 13 cases were treated with open surgery (including one secondary open operation after thoracoscopic operation). The average size of mediastinal tumors was 2.17±1.22 cm. For the post-operational pathology, 16 cases (76.2%) were diagnosed as ectopic parathyroid adenoma; 4 cases (19.0%) were diagnosed as parathyroid hyperplasia, while only 1 case (4.8%) was diagnosed as parathyroid adenocarcinoma.

Conclusions: Parathyroid adenoma accounts for the major pathological type of ectopic mediastinal parathyroid tumors. In addition, the correct diagnosis with precise preoperative location was the key for the treatment of ectopic mediastinal parathyroid tumors accompanied with hyperparathyroidism. Surgical intervention was demonstrated to be an effective way for the treatment of ectopic mediastinal parathyroid tumors with satisfied therapeutic outcome, especially for the VATS due to its unique clinical advantages. However, there may some difficulties when locating ectopic mediastinal parathyroid tumor less than 1 cm and the operators should be very cautious when performing thoracoscopic operations.
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http://dx.doi.org/10.21037/jtd.2017.11.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757062PMC
December 2017

Robotic thoracic surgery: S1+2 segmentectomy of the left upper lobe: advantage of robotic assisted thoracic surgery.

J Thorac Dis 2017 Oct;9(10):E973

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.

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http://dx.doi.org/10.21037/jtd.2017.10.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723753PMC
October 2017

Robotic-assisted right upper lobectomy: with the further research, robot-assisted thoracic surgery (RATS) will be better in future.

J Thorac Dis 2017 Oct;9(10):E964-E965

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

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http://dx.doi.org/10.21037/jtd.2017.10.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723851PMC
October 2017

Beclin 1 expression is associated with the occurrence and development of esophageal squamous cell carcinoma.

Oncol Lett 2017 Dec 21;14(6):6823-6828. Epub 2017 Sep 21.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Beclin 1 has a central role in the regulation of autophagy, differentiation, apoptosis resistance, tumorigenesis and cancer progression. The role of Beclin 1 in the development of esophageal squamous cell carcinoma (ESCC) and its subsequent progression is not fully characterized. In the present study, the role of Beclin 1 and autophagy in ESCC was evaluated. The expression of Beclin 1 mRNA and protein levels in human ESCC tumor and adjacent normal esophageal tissue was measured. Beclin 1 mRNA and protein were significantly lower in tumor tissue than in normal esophageal tissue (P<0.05). Cells of the less differentiated esophageal tumors expressed lower Beclin 1 mRNA and protein (P<0.05). Tumors from patients in early clinical stages (I/II) exhibited significantly higher Beclin 1 mRNA and protein expression levels than patients with tumors in mid-to-late stages (III/IV; P<0.05). Tumors from patients with lymph node metastasis exhibited significantly lower Beclin 1 mRNA and protein expression levels compared with tumors from patients without lymph node involvement (P<0.05). Beclin 1 downregulation was demonstrated to significantly upregulate invasion by ESCC EC9706 cells (P<0.01), and downregulate the number of acidic vesicular organelles, a process associated with autophagy. These results suggest that the expression of Beclin 1 is associated with the occurrence and development of ESCC. Measuring the Beclin 1 expression of tumors from patient may improve the understanding of the prognosis of patients with ESCC.
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http://dx.doi.org/10.3892/ol.2017.7015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686516PMC
December 2017

ATG7 deficiency promote apoptotic death induced by Cisplatin in human esophageal squamous cell carcinoma cells.

Bull Cancer 2013 Jul-Aug;100(7-8):15-21

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China.

Cisplatin-(DDP)-based adjuvant chemotherapy is widely used for the treatment of esophageal cancer. However, DDP-based combinatorial treatments can eventually result in tumor resistance response. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored. In this study, we aimed to understand the role of autophagy in ESCC cells resistance to Cisplatin and discuss its potential therapeutic implication. We found that exposure to Cisplatin induced a significant increase in LC3 formation. While the proliferation of ESCC cells was inhibited upon Cisplatin exposure, inhibition of autophagy by ATG7 interference further increased the sensitivity to chemotherapy. Meanwhile, the Cisplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in ESCC cells resistance to Cisplatin. Intriguingly, the resistance could be recovered by autophagy inhibition. This also points to potential therapy for ESCC by perturbing autophagy.
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http://dx.doi.org/10.1684/bdc.2013.1749DOI Listing
September 2013

The different induction mechanisms of growth arrest DNA damage inducible gene 45 β in human hepatoma cell lines.

Chemotherapy 2012 2;58(2):165-74. Epub 2012 Jun 2.

Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aims: Downregulation of the growth arrest and DNA damage-inducible gene 45 β (GADD45β) has been verified to be specific to HCC and consistent with the degree of malignancy. The differences in induction mechanisms of GADD45β were investigated based on transcriptional regulation.

Methods: Following our published data from S-adenosylmethionine (SAMe), oxaliplatin and sorafenib were further used to stimulate GADD45β expression in cultured HepG2 (p53 wild type) and Hep3B (p53 null) hepatoma cells in vitro. The different effects on cell viability, DNA synthesis and caspase activities were also measured.

Results: Oxaliplatin and sorafenib could induce GADD45β in both HepG2 and Hep3B in a dose-dependent manner with rapid and direct cytotoxic effect. Transcriptional activity of NF-ĸB and E2F-1 were both enhanced by oxaliplatin and sorafenib. However, SAMe could only induce GADD45β in HepG2 through the NF-ĸB pathway, resulting in a slow and indirect cytotoxic effect. Although all three inducers could lead to a pronounced rise in caspase activities, only high concentration of SAMe could inhibit DNA synthesis as significantly as the chemo drugs. No apparent changes in GADD45β induction, promoter activity or cytotoxic effects were observed in Hep3B(+p53) when treated with oxaliplatin and sorafenib, while relatively significant changes occurred with SAMe.

Conclusion: GADD45β induction is a novel mechanism of SAMe-mediated hepatoprotection with p53 involvement.
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http://dx.doi.org/10.1159/000338386DOI Listing
October 2012

Emerging role of autophagy during ischemia-hypoxia and reperfusion in hepatocellular carcinoma.

Int J Oncol 2012 Jun 26;40(6):2049-57. Epub 2012 Mar 26.

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Hepatocellular carcinoma (HCC) is the most common primary malignancy found in the liver. Autophagy is the intracellular bulk degradation process for long-lived proteins and dysfunctional organelles. In this study, we report that autophagy plays a role in HCC cell proliferation in response to ischemia-hypoxia (I/H) and reperfusion and discuss its potential therapeutic implications. By establishing a simulated model in cultured HepG2 (p53 wild-type) and Hep3B (p53 null) hepatoma cells in vitro, we found that exposure to I/H induced a significant increase in microtubule-associated protein 1 light chain 3 (LC3) lipidation and subsequent LC3 puncta formation. While the proliferation of HCC cells was stimulated upon acute I/H exposure compared to that of control, inhibition of autophagy by autophagy-related protein 7 interference abolished it. In addition, the steady-state levels of sequestosome 1 (p62) in both HepG2 and Hep3B cells were reduced following I/H exposure, supporting the notion that acute I/H induces autophagy. Intriguingly, the p62 level further decreased during reperfusion following I/H, accompanied by increased LC3 lipidation. The intracellular reactive oxygen species (ROS) accumulated during acute I/H exposure and persisted through reperfusion in both HepG2 and Hep3B cells and the ROS levels increased at a much faster rate during reperfusion than during I/H periods in both cells. Autophagy functions as a promoter for HCC cell survival during acute I/H and reperfusion and this also points to potential therapy for hepatoma by perturbing the acute I/H-reperfusion-autophagy axis.
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http://dx.doi.org/10.3892/ijo.2012.1415DOI Listing
June 2012

Role of autophagy in resistance to oxaliplatin in hepatocellular carcinoma cells.

Oncol Rep 2012 Jan 20;27(1):143-50. Epub 2011 Sep 20.

Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.

In spite of an initially promising anti-tumor activity, oxaliplatin-based combinatorial treatments can eventually result in a tumor resistance response. In this study we aimed to understand the role of autophagy in HCC cell resistance to oxaliplatin and to discuss its potential therapeutic implication. We found that exposure to oxaliplatin induced a significant increase in LC3 lipidation and subsequent LC3 puncta formation. While the proliferation of HCC cells was inhibited upon oxaliplatin exposure, inhibition of autophagy by ATG7 interference and chloroquine pre-treatment further increased the sensitivity to chemotherapy. Meanwhile, the oxaliplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in HepG2 cell resistance to oxaliplatin. Intriguingly, the resistance could be recovered apparently by inhibition of autophagy. This also points to the potential therapy for hepatoma by perturbing autophagy.
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http://dx.doi.org/10.3892/or.2011.1464DOI Listing
January 2012