Publications by authors named "Lianggang Zhu"

8 Publications

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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

Home enteral nutrition for postoperative elderly patients with esophageal cancer.

Ann Palliat Med 2021 Jan;10(1):278-284

Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Email:

Background: The clinical value of enteral nutrition (EN) after radical resection of esophageal cancer (EC) has been well recognized during hospital stay; however, whether using EN agents should be continued at home after the patient is discharged remains unclear, especially for the elderly postoperative patients. Here we investigated the effects of continued EN on nutrition and immune status in elderly patients who had undergone radical EC surgery.

Methods: Sixty eligible elderly patients undergoing surgical treatment for EC in our center during the period from October 2016 to October 2018 were randomly divided into EN group and control groups, with 30 patients in each group. Among them, the EN group continued to take an orally administered EN agent (Ensure®) daily in addition to daily routine diets after discharge; however, patients in the control group only received regular diets after discharge. The nutritional status and immune indicators were evaluated at discharge and 4 and 8 weeks after discharge (weeks 4 and 8) and compared between EN and control groups.

Results: Body mass index (BMI), Patient-Generated Subjective Global Assessment (PG-SGA) score, hemoglobin, serum albumin, serum prealbumin, CD4 and CD8 T cell counts, CD4/CD8 ratio, IgA, IgG, and IgM showed no significant difference between EN group and control group at discharge (all P>0.05). In week 4, the serum prealbumin level was significantly higher in the EM group than in the control group (P<0.05). In week eight, the EM group had significantly higher BMI, PG-SGA score, serum albumin, serum prealbumin, CD4 and CD8 T cell counts, CD4/CD8 ratio, IgA, IgG, and IgM than the control group (all P<0.05).

Conclusions: Home EN helps improve immune function in elderly patients who have undergone radical surgery for EC and is worthy of clinical promotion. To optimize its efficacy, a home EN should last no less than eight weeks after discharge.
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http://dx.doi.org/10.21037/apm-20-2197DOI Listing
January 2021

Endoscopic injection of human fibrin sealant in treatment of intrathoracic anastomotic leakage after esophageal cancer surgery.

J Cardiothorac Surg 2020 May 14;15(1):96. Epub 2020 May 14.

Department of Thoracic Surgery, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, 201801, China.

Objective: To investigate the application of endoscopic injection of human fibrin sealant in treatment of patients with intrathoracic anastomotic leakage after esophagectomy.

Methods: A total of 179 patients who underwent intrathoracic anastomosis after esophageal cancer surgery in our department From December 2012 to May 2015 were retrospectively analyzed. The clinical data and treatment of 7 patients with postoperative intrathoracic anastomotic leakage were analyzed and discussed. On Day 28 after operation, the 7 patients were given endoscopic injection of human fibrin sealant to seal the anastomotic leakage, and the changes in drainage volume, body temperature, CRP, white blood cell count and other indicators were compared before and after endoscopic intervention.

Results: After endoscopic injection of human fibrin sealant in all 7 patients with intrathoracic anastomotic leakage, the volume of para-anastomotic drainage, CRP, and WBC count were improved compared with those before treatment. Relevant data were analyzed, and the differences were statistically significant (P = 0.019, P = 0.001, P = 0.014, respectively). No statistically significant difference was observed in the body temperature before and after treatment (P = 0.217).

Conclusion: For patients with intrathoracic anastomotic leakage after esophageal cancer surgery, endoscopic injection of human fibrin sealant to seal the anastomotic leakage has positive therapeutic effects of reducing exudation around the anastomotic leakage, reducing systemic inflammatory response, and improving clinical symptoms including dysphagia, weight loss without trying, chest pain, pressure or burning, worsening indigestion or heartburn and coughing or hoarseness.
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http://dx.doi.org/10.1186/s13019-020-01127-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227310PMC
May 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

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