Objective To explore the role of versican (VCAN) in ESCC prognosis based on bioinformatics data. MethodsFirst, three RNA microarray datasets of ESCC were downloaded from GEO database, which were then integrated and used to explore differentially expressed genes (DEGs). The subsequent analysis was conducted based on the results of these DEGs: (1) The STRING database was used to construct a protein-protein interaction (PPI) network; (2) molecular complex detection software was used to analyze the modules of the PPI network, of which the most significant modules were chosen, and hub genes were the genes included in the chosen modules; (3) high-throughput RNA sequencing data from TCGA and GTEx databases were used to verify the expression of these hub genes to confirm whether they were differentially expressed; (4) the survival curve analysis of confirmed DEGs was conducted to select genes that had significant influence on the survival of ESCC; (5) TIMER database was used to analyze the relationship between the gene expression of VCAN and the abundance of tumor-infiltrating immune cells (TIICs) and gene markers in these cells; (6) Targetscan and miRDB software were used to predict the miRNAs that could regulate VCAN, and Cytoscape software was used to construct the regulatory network. ResultsA total of 630 DEGs and 32 hub genes were found, of which VCAN was an up-regulated DEG, and high expression of VCAN was significantly associated with poor prognosis of ESCC. Moreover, VCAN could also play a role in the immune microenvironment of ESCC, which was mainly manifested by a significant positive correlation between the abundance of VCAN and the abundance of M2 macrophages gene markers, some of which had been reported to be associated with poor prognosis of ESCC. Finally, we also found that VCAN could be regulated by 15 miRNAs in ESCC, some of which had been reported to be associated with ESCC prognosis. ConclusionThis study provides direct and indirect comprehensive evidence for the role of VCAN in ESCC prognosis. The direct evidence is that the survival curve shows that highly expressed VCAN is significantly associated with the poor prognosis of ESCC, and the indirect evidence is that VCAN is positively related to some markers which indicate poor prognosis in the ESCC immune microenvironment, and VCAN can be regulated by some prognostic miRNAs in ESCC.
Objective To analyze the efficacy of and recurrence mode after adjuvant radiotherapy for lower thoracic esophageal squamous cell carcinoma (TESCC) patients after radical operation with anastomosis above aortic arch. Methods Sixty-three patients with lower TESCC who received adjuvant radiotherapy after R0 radical operation with anastomosis above aortic arch between February 2011 and February 2019 were retrospectively enrolled. The clinical tumor volume (CTV) included anastomotic stoma, and lymph node drainage area in mediastinum and upper abdomen. The survival status, recurrence and metastasis of tumors, and the influencing factors were analyzed. Results The 1-, 2-, and 3-year overall survival rates were 98.3%, 83.3%, and 63.7%, respectively. The median disease-free survival (DFS) was 33 months [95% confidence interval (23.2, 42.8) months], and the 1-, 2-, and 3-year DFS rates were 76.3%, 58.5%, and 41.7%, respectively. Patients with N0-1 had longer DFS than those with N2-3 (median: not reached vs. 15 months, P=0.045). The recurrence rate of anastomotic site was 7.9%. The recurrence rates of lymph nodes in supraclavicular region, upper middle mediastinum, and upper abdomen were 4.8%, 15.9%, and 1.6%, respectively. The distant metastasis rate was 17.5%. The incidence of grade 2-3 radiation pneumonitis, grade 3 anastomotic stenosis, and grade 3 tracheal fistula were 4.8%, 3.2%, and 1.6%, respectively. Conclusions N2-3 is a poor prognostic factor for such patients. Regional lymph node recurrence is mainly revealed in the middle and upper mediastinum. Whether the CTV should include anastomotic stoma and lymph node drainage area in lower mediastinum and upper abdomen is questionable.
Increasing evidence suggests that many types of cancers contain a population of cells that display stem cell properties. These cells are called cancer stem cells （CSCs），which are closely related to tumor initiation，growth，metastasis and chemoresistance. CSCs are also found in esophageal squamous cell carcinoma （ESCC）. These cells are characterized by potential of self-renewal and differentiation，tumor formation in nude mice and chemotherapy resistance，and thus may play an important role in targeted cancer therapies. Current methods for culturing and sorting CSCs in ESCC mainly include fluorescence activated cell sorting （FACS），magnetic activated cell sorting （MACS），suspension culture，and side population （SP） cell sorting. In this review，we focus on current research methods for CSCs in ESCC，their biological characteristics and areas for improvement. We believe that a combination of multiple cell-surface makers is needed for research of CSCs in ESCC.
ObjectiveTo investigate the short-term therapeutic effect of neoadjuvant immunotherapy combined with chemotherapy in the locally advanced esophageal squamous cell carcinoma. MethodsThe clinical data of patients with esophageal squamous cell carcinoma treated with neoadjuvant treatment in Gaozhou People's Hospital from August 2019 to October 2020 were retrospectively analyzed. According to the different treatments, the patients were divided into two groups: a neoadjuvant immunotherapy combined with chemotherapy group (NIC group) and a neoadjuvant chemoradiotherapy group (NC group). The baseline data, incidence of adverse events during treatment, perioperative indicators, postoperative pathological remission rate and incidence of postoperative complications were compared between the two groups. ResultsTotally 33 patients were enrolled, including 15 males and 18 females, with an average age of 62.37±7.99 years. There were 17 patients in the NIC group and 16 patients in the NC group. In the NIC group, the carcinoma was mainly located in the middle and lower esophagus, with 5 paitents in stage Ⅱ, 9 patients in stage Ⅲ, and 3 patients in stage Ⅳa. In the NC group, the carcinoma was mainly located in the upper-middle esophagus, with 1 patient in stage Ⅱ and 15 patients in stage Ⅲ. During the neoadjuvant treatment, there was no significant difference in the occurrence of bone marrow suppression or gastrointestinal reactions between the two groups (P>0.05). There were 4 immune-related rashes in the NIC group and 1 esophageal perforation in the NC group. Fourteen (82.35%) patients in the NIC group and 12 (75.00%) patients in the NC group completed the operation on schedule. The postoperative ICU stay time and chest tube indwelling time in the NIC group were shorter than those in the NC group (P<0.05). There were 5 patients of complete remission in the NIC group, and 6 patients in the NC group. There was no significant difference in the pathological regression grade or residual tumor cells between the two groups (P>0.05). There was no significant difference in the incidence of anastomotic fistula, thoracic gastric fistula, bronchial mediastinal fistula, abdominal distension, pulmonary infection, stroke, or hoarseness during the perioperative period between the two groups of patients who completed the operation (P>0.05). In the NC group, 2 patients died during the perioperative period because of thoracic gastric fistula complicated by severe infection. ConclusionNeoadjuvant immunotherapy combined with chemotherapy dose not significantly increase the occurrence of adverse events and shows a good rate of pathological remission, which indicates that the neoadjuvant immunotherapy combined with chemotherapy is a safe, feasible and potential new treatment model.
ObjectiveTo explore the expression of vascular endothelial growth factor receptor-2(VEGFR-2) protein in esophageal squamous cell carcinoma (ESCC) and to analyze the relationship between VEGFR-2 and prognostic of esophageal cancer in Uygur of Xinjiang. MethodsThe expression of VEGFR-2 protein including 72 patients with ESCC[with 56 males and 16 females at age of 57 (43-79) years] and paracarcinomatous tissues of 28 patients were detected by immunohistochemistry staining (SP) between January 2007 and september 2009 in this hospital. The Kaplan-Meier and Cox proportional hazards analysis were used to analyze the prognosis of ESCC. ResultsThe positive expression rate of VEGFR-2 protein in 72 patients with ESCC was 80.56% (58/72) and 0 in paracarcinomatous tissues. The expression of VEGFR-2 protein in the ESCC was much higher than that in paracarcinomatous tissues with a statistical difference (P<0.05). The expression of VEGFR-2 protein was significantly correlated with depth of invasion, lymph node metastasis, distant metastasis and TNM staging (P<0.05). Tumor size was no correlation with expression of VEGFR-2 protein (P>0.05). Kaplan-Meier survival analysis indicated that five-year survival rate in positive expression of VEGFR-2 was higher than that in the negative group. Lymph node metastasis, TNM staging, and the positive expression of VEGFR-2 protein were independent prognostic factors. ConclusionVEGFR-2 protein is expressed more in ESCC and might be used as the index to predict prognosis and metastasis of esophagedal carcinoma in Uygur.
ObjectiveTo compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. MethodsA retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. ResultsA total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. ConclusionCompared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.
Objective To investigate the prognostic value of preoperative inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and fibrinogen-to-prealbumin ratio (FPR), for postoperative survival in patients with resectable esophageal squamous cell carcinoma (ESCC). Additionally, to construct and validate a prognostic model for ESCC based on these inflammatory markers combined with TNM staging. Methods We retrospectively analyzed the clinical data of patients with histologically confirmed ESCC who underwent surgical resection at the First Affiliated Hospital of the University of Science and Technology of China during 2017. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for preoperative NLR, PLR, SII, and FPR. Clinicopathological characteristics were compared between patient groups with different levels of these markers. Survival analysis was performed using the Kaplan-Meier method, and univariate and multivariate regression analyses were conducted using the Cox proportional hazards model to identify prognostic factors. Nomograms for predicting overall survival (OS) and disease-free survival (DFS) were constructed using R software. The model's discrimination was assessed with ROC curves, its calibration was evaluated with calibration curves, and its clinical utility was determined by decision curve analysis (DCA). Results A total of 224 patients who underwent surgery for ESCC were included, comprising 180 males and 44 females. The optimal preoperative cut-off values of NLR, PLR, SII, and FPR for predicting postoperative OS were 2.70, 140.34, 360.73, and 0.015, respectively. The 5-year OS and DFS rates in the high-NLR group were lower than in the low-NLR group (both P<0.001). Similarly, patients in the high-PLR group (P=0.005 and P=0.009, respectively), high-SII group (P=0.008 and P=0.018, respectively), and high-FPR group (both P<0.001) had lower 5-year OS and DFS rates compared to their low-level counterparts. Multivariate Cox regression analysis revealed that patient age, T stage, N stage, tumor differentiation, and NLR>2.70 et al were independent prognostic factors for both OS and DFS. Based on these factors, nomograms for OS and DFS were constructed. The area under the ROC curve (AUC) for 3- and 5-year OS were 0.966 and 0.907, respectively, and for 3- and 5-year DFS were 0.960 and 0.919, respectively. The calibration curves showed good agreement between predicted and actual outcomes. DCA demonstrated that the models provided a positive net benefit for all patients under intervention. Conclusion Preoperative levels of NLR, PLR, SII, and FPR are associated with the prognosis of patients with ESCC, with NLR being an independent prognostic predictor. The nomogram models, constructed based on patient age, tumor differentiation, T stage, N stage, and preoperative NLR level, can accurately predict the prognosis of patients with ESCC. These models may help guide preoperative clinical decision-making and tailor treatment and follow-up strategies.
Objective To investigate the expression and clinical significance of CXCR4 in esophageal squamous cell carcinoma (ESCC). Methods Databases including PubMed, EMbase, Web of Science, CBM, VIP, CNKI and WanFang Data were searched from inception to April 2012, and the relevant references were also retrieved to collect relevant case-control studies. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the quality of the included studies. Then the meta-analysis was conducted using RevMan 5.1 software. Results A total of 5 case-control studies involving 493 ESCC tissues and 136 normal esophageal tissues were included. The results of the meta-analyses showed that, as for the positive rate of CXCR4 expression, it was higher in ESCC tissues rather than normal esophageal tissues (OR=12.03, 95%CI 6.76 to 21.44, Plt;0.000 01), in ESCC tissues with lymph node metastasis rather than those without lymph node metastasis (OR=4.35, 95%CI 2.48 to 7.62, Plt;0.000 01), as well as in moderate and low differentiated ESCC tissues rather than high differentiated ESCC tissues (OR=0.51, 95%CI 0.32 to 0.81, P=0.004); but no significant difference was found between the clinical stage I-II and clinical stage III-IV ESCC tissues. Conclusion The presently limited evidence shows CXCR4 expression is associated with ESCC, lymph node metastasis and degree of cell differentiation, indicating that CXCR4 may take a role in the whole course of carcinogenesis of ESCC. But the relationship between CXCR4 expression and clinical stage of ESCC is still unclear, which needs to be further proved by more large-scale, well-designed and high quality case-control studies.
ObjectiveTo investigate the relationship between DDX46 genes and invasion and migration of esophageal squamous cell carcinoma cells. MethodsHuman esophageal squamous cell carcinoma cells TE-1 were transfected by fluorescent marker shRNA lentivirus (shDDX46 group), and an empty vector was transfected as a control (shCtrl group). The expression rate of green fluorescent protein under the microscope was used to evaluate the cell transfection efficiency. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blotting (WB) detected the knockdown efficiency of the target gene at the mRNA and protein expression levels. Wound healing, invasion assay and migration assay detected the changes of invasion and metastasis ability. Classical pathway analysis was used to explore signaling pathway changes and the possible mechanism of DDX46 in the invasion and metastasis was explored by detecting fibronectin expression. ResultsDDX46 gene at mRNA and protein levels was significantly inhibited after lentiviral transfection. Wound healing showed that after 8 h the cell mobility of TE-1 cells decreased significantly (P=0.001). Invasion assay showed that after 24 h the average cell metastasis rate of TE-1 cells was lower in the shDDX46 group than that in the shCtrl group (P<0.001). The cell metastasis rate in the shDDX46 group corresponding to observation points in the transwell assay was lower than that in the shCtrl group (P<0.001) after 24 h culture. The results of the classical pathway analysis showed that the integrin signaling pathway activity was inhibited, further exploration of the mechanism of action found that the expression of fibronectin associated with cell adhesion was decreased. ConclusionDDX46 gene is related to the invasion and migration ability of esophageal squamous cell carcinoma cells. Knockdown of DDX46 genes may reduce cell adhesion by downregulating the integrin pathway signaling.
Objective To investigate the clinical significance and expression of T helper cell secretory cytokines in esophageal squamous cell carcinoma tissues, which provide theoretical basis of reasonable and effective therapy for patients with esophageal carcinoma. Methods Fifty-six specimens of patients who underwent esophageal carcinoma resection were divided into two groups. Group A (n=28) included grade Ⅰand Ⅱ specimens of esophageal squamous cell carcinoma, group B (n=28) included grade Ⅲ and Ⅳ specimens of esophageal squamous cell carcinoma. Control group included 6 specimens of esophagitis. The expression of tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10) and transforming growth factor beta (TGF-β) in all specimens were detected. Results The positive expression of TNF-α,TGF-β and IL-10 in group A and group B were significantly higher than those in control group(Plt;0.01); the positive expression of TNF-α in group A was higher than that in group B, while the positive expression of TGF-β and IL-10 were lower than those in group B (Plt; 0.01). There was negative correlation between the positive expression of TNF-α and IL-10, TGF-β(Plt;0.01), and positive correlation between TGF-β and IL-10 (Plt; 0.01). The positive expression of TNF-α in patients of survival period in 3 years was lower than that exceed 3 years(F=36.25 ,Plt;0.01),while the positive expression of IL-10 and TGF-β in the patients of survival period in 3 years were higher than those exceed 3 years(F=29.29,26.69;Plt;0.01). Conclusion By the way of changing the level of cytokines secretion from T helper cells, esophageal squamous cell carcinoma tissues destroyed the balanced condition of patient’s immune system, which made esophageal carcinoma tissues escape the attack from the patient’s immune system and promote the invasion into surrounding tissues.