Development and validation of a prognostic model based on RNA binding proteins in patients with esophageal cancer.

Background: RNA-binding proteins (RBPs) play a crucial role in regulating RNA turnover and are associated with cancer development. However, little is known about the role of RBPs in esophageal cancer (ESCA). The present study focuses on the association between RBP gene expression and survival in ESCA, addressing the clinical relevance of an RBPs-based prediction model for prognosis. Methods: RNA-sequencing data and clinical information of patients with ESCA were obtained from The Cancer Genome Atlas (TCGA) database. We identified differentially expressed genes in ESCA and intersected them with RBP-encoding genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with the identified differentially expressed RBPs. Then, a protein-protein interaction (PPI) network was constructed through the STRING database to determine the hub RBPs. Univariate Cox regression analysis and multivariate Cox regression analysis were applied to construct a novel prognostic model based on RBPs. Based on the R package "Caret", we divided patients into the training set and validation set. The efficacy of the prognostic model was evaluated by the area under the receiver operating characteristic (ROC) curve. A nomogram was developed for the prediction of patient survival outcomes. Results: A total of 158 ESCA patients from the TCGA database were included in our analysis. We screened out five prognostic RBPs (CLK1, CIRBP, MRPL13, TNRC6A, and TYW3) through univariate and multivariate Cox regression analysis. CLK1, CIRBP, TNRC6A and TYW3 were downregulated in tumor samples, while MRPL13 was upregulated. A prognostic model constructed with these five RBPs in the training data set accurately stratified ESCA patients into high- and low-risk groups. When the same prognostic model was applied to the test data set and entire cohort, the 5-RBP signature remained an independent prognostic factor in multivariate analysis. The areas under the time-dependent ROC curve of the prognostic model for predicting one-year survival in the training data set, test data set, and entire cohort were 0.789, 0.753, and 0.764, respectively, confirming that this model is a good prognostic model. The nomogram based on the five RBPs and clinical variables could improve individualized outcome predictions and highlight the importance of RBPs in the outcomes of patients with ESCA. Conclusions: Our study provides a potential prognostic model for predicting the prognosis of ESCA patients. The prognostic nomogram could improve individualized outcome predictions for patients with ESCA, therefore providing novel insights into future diagnosis and treatment.

High-dimensional single-cell proteomics analysis of esophageal squamous cell carcinoma reveals dynamic alterations of the tumor immune microenvironment after neoadjuvant therapy.

BACKGROUND: Dynamic alterations of the tumor immune microenvironment in esophageal squamous cell carcinoma (ESCC) after different neoadjuvant therapies were understudied. METHODS: We used mass cytometry with a 42-antibody panel for 6 adjacent normal esophageal mucosa and 26 tumor samples (treatment-naïve, n=12; postneoadjuvant, n=14) from patients with ESCC. Single-cell RNA sequencing of previous studies and bulk RNA sequencing from The Cancer Genome Atlas were analyzed, flow cytometry, immunohistochemistry, and immunofluorescence analyses were performed. RESULTS: Poor tumor regression was observed in the neoadjuvant chemotherapy group. Radiotherapy-based regimens enhanced CD8+ T cells but diminished regulatory T cells and promoted the ratio of effector memory to central memory T cells. Immune checkpoint blockade augmented NK cell activation and cytotoxicity by increasing the frequency of CD16+ NK cells. We discovered a novel CCR4+CCR6+ macrophage subset that correlated with the enrichment of corresponding chemokines (CCL3/CCL5/CCL17/CCL20/CCL22). We established a CCR4/CCR6 chemokine-based model that stratified ESCC patients with differential overall survival and responsiveness to neoadjuvant chemoradiotherapy combined with immunotherapy, which was validated in two independent cohorts of esophageal cancer with neoadjuvant treatment. CONCLUSIONS: This work reveals that neoadjuvant therapy significantly regulates the cellular composition of the tumor immune microenvironment in ESCC and proposes a potential model of CCR4/CCR6 system to predict the benefits from neoadjuvant chemoradiotherapy combined with immunotherapy.

The prognostic value of an immune-related gene signature and infiltrating tumor immune cells based on bioinformatics analysis in primary esophageal cancer.

Background: Immunotherapy is a promising novel treatment for esophageal cancer (ESCA). However, previous studies provide limited direct information about the prognostic significance of immune-related genes (IRGs) in primary ESCA development. This study explored the prognostic value of IRGs and infiltrating tumor immune cells in primary ESCA. Methods: The ribonucleic acid (RNA)-sequencing data and clinical information of primary ESCA were downloaded from The Cancer Genome Atlas (TCGA) database. Which included the clinical factors and prognosis outcomes of the ESCA patients. The IRGs were downloaded from the ImmPORT database. Results: We established the robust IRG prognostic signature of 4 IRGs (i.e., heat shock protein family A member 6, Oncostatin M, androgen receptor, and nuclear receptor subfamily 2 group F member 2) in primary ESCA, and divided the ESCA patients into high- and low-risk groups based on overall survival (OS). The Kaplan-Meier curves showed the high predictive ability of the prognostic signature in the training, testing, and full data sets (P=2.407e-03, P=1.044e-02, and P=2.535e-04, respectively). Multivariate Cox regression analyses were performed with age, grade, tumor stage, tumor type and the risk score as covariables. The risk score supports the use of a prognostic signature as an independent prognostic factor [training data set: hazard ratio (HR) =1.185, 95% confidence interval (95% CI): 1.013-1.388, P=0.034; testing data set: HR =2.056, 95% CI: 1.015-4.166, P=0.045; full data set: HR =1.197, 95% CI: 1.059-1.354, P=0.004]. The area under the curve (AUC) of the receiver operating characteristic curve validated the high predictive accuracy of the IRG signature in the training, testing, and full data set (AUCs =0.808, 0.657, and 0.751, respectively). The infiltration level of the activated mast cells was significantly higher in the high-risk group than the low-risk group; thus, infiltrating mast cells are associated with worse OS in ESCA patients. Conclusions: Our IRG prognostic signature provides a new direction to predict the survival of primary ESCA patients and has the potential ability to establish, promote, and improve personalized treatment procedures based on each patient's risk.

Single-port combined subsegment resection (RS3b + S1bi) with a rare branching segment pattern of the bronchi and vessels: case report and literature review.

Background: Video-assisted thoracoscopic surgery segmentectomy is increasingly being used to resect peripheral small lung cancer. However, to manage some lesions which locate between segment deep inside the parenchyma is still challenging. Generally, wedge resection and segmentectomy are optional for peripheral small lung cancer. However, it is hard to achieve safe surgical margins if the lesion is located in the segment plane deep inside the parenchyma, especially close to the segment hilum. In that situation, lobectomy and bi-segmentectomy are usually performed for the sake of safe margins with the price of excessive normal lung tissue lost. To ensure safe surgical margins and preserve normal lung tissue as far as possible, combined subsegmentectomy is feasible and it is required precise preoperative plan including surgical margin delineation, bronchi and vessels variation and surgical procedure. The variation of bronchi and segment vein in our current case are rare and the branching pattern of pulmonary artery-inferior trunk (Tr.inf) is firstly reported in our case. Case Description: In 2019, a 41-year-old female presented to the Thoracic Clinic with a history of a 7-mm sized, mixed-density ground-glass opacity (GGO) in the right upper lobe. The lesion located in the segmental plane between S3b and S1b deep inside the parenchyma. We performed precise preoperative planning with 3-dimension pulmonary bronchi and vessels reconstruction and resected RS3b + S1bi via single-port approach. The patient was discharged from hospital on the 5th postoperative day without any complications. Chest computed tomography (CT) scans in the 12th and 24th months after surgery showed good lung recovery, and no atelectasis or pulmonary congestion was observed. Notably, we observed a new branching pattern of A1b, which came from the inferior trunk, combined with A3a. Additionally, we performed a literature review to analyze the variation patterns of segmental structures in the right upper lobe, and the indications, effects, and safety of combined subsegmentectomy. Conclusions: Our case and review of literature showed that combined subsegmentectomy was feasible for lesion deep inside parenchyma if a detailed preoperative plan and delicate procedures during surgery were implemented.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Management of middle lobe veins during single-portal video-assisted thoracoscopic surgery lobectomy via the fifth intercostal approach (case series): why the subcarinal triangular right base angle is helpful.

Background: The fifth intercostal space is the preferred approach during uniportal video-assisted thoracoscopic surgery (VATS) lobectomy. However, managing the right middle lobe pulmonary vein (RML PV) through this approach is technically challenging for inexperienced surgeons. To facilitate the surgical procedure, we describe our surgical strategy for managing the middle lobe vein via the fifth intercostal space and define the approach [subcarinal triangular right base angle (SCT-RBA)] utilized to manage the middle lobe vein. Case Description: Based on the characteristics of uniportal surgery, we designed a new method of managing middle lobar veins via the fifth intercostal approach, which also facilitates the dissection of the subcarinal lymph nodes. We described the short-term surgical outcomes of 7 patients who underwent single-port middle lobe resection from January 2021 to January 2022 in the Department of Thoracic Surgery, Ruijin Hospital North Campus, Shanghai Jiaotong University School of Medicine. No conversion and mortality were observed in 7 patients who underwent single-port VATS middle lobe resection. One patient had bronchial asthma and air leakage, which led to delayed drainage and hospitalization. There were no complications or delayed discharge reported among the other patients. Conclusions: Our initial results indicate that this new technique is a feasible strategy to manage the middle lobe veins and facilitate the dissection of subcarinal lymph nodes.

Beclin-1 is a Promising Prognostic Biomarker in a Specific Esophageal Squamous Cell Carcinoma Population.

The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues (p < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern (p < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant (p > 0.05), whereas Beclin-1 expression was significantly associated with OS (p < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.

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

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 (P<0.05), and higher Masaoka stages (P<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (P<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.

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

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 (DNAJB1, BNIP1, VAMP7 and TBK1) 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.

Home enteral nutrition for postoperative elderly patients with esophageal cancer.

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.

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

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.

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

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.

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

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.

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

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.

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

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.