Objective To explore the expression of CD105 protein in esophageal squamous cell carcinoma and it＇s relationship with P53 protein. Methods Using streptavidin biotinperoxidase （SP） method, the expression of CD105 protein and P53 protein in esophageal squamous cell carcinoma were examined in normal esophageal tissues （n=10） and esophageal squamous cell carcinoma tissues（n=86）. Results The expression positive rate of CD105 protein was 74. 4%（64/86） in esophageal squamous cell carcinoma , 0% in normal esophageal epithelium. Expression positive rate of CD105 protein was 66. 1%（37/56） in early stage （stage Ⅰ-Ⅱ ）, 90.0% （27/30） in later stages （stage Ⅲ-Ⅳ ）. The expression of CD105 protein were bly associated with P53 protein（P〈0. 05）. Conclusion CD105 protein may participate in the onset and progression of esophageal squamous cell carcinoma. CD105 protein could he a new diagnostic /therapeutic target in esophageal squamous cell carcinoma.
ObjectiveTo explore the effect of DDX46 silencing on growth and apoptosis in esophageal squamous cell carcinoma cell TE-1 by the shRNA. MethodsThe relative expression of DDX46 mRNA in TE-1 cells was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and compared with immortalized human esophageal squamous cell Het-1A. DDX46 shRNA-expressing lentivirus was applied to silence DDX46 (experimental group), and non-silencing control lentivirus was added (control group) with a multiplicity of infection of 5 in TE-1 cells. In both groups, cell growth was monitored using high content screening, cell colony-forming capacity was measured by colony formation assay, cell apoptosis were determined by flow cytometry. Further, the Stress and Apoptosis Signaling Antibody Array Kit was used to detect the changes of signaling molecules in TE-1 cells after DDX46 knockdown. ResultsCompared with the control group, cell counting after DDX46 silencing showed that TE-1 cell growth was significantly inhibited (P<0.001). Colony formation assay showed that cell colony-forming capacity was significantly inhibited (P<0.01). Annexin V-APC flow cytometry showed a significant increase in apoptosis (P<0.001). In PathScan® Antibody Array, the expression levels of Akt (Ser473, phosphorylation) and IκBα (Total, N/A) significantly decreased (P<0.01), and the expression of Caspase-3 (Asp175, cleaved) increased (P<0.05). ConclusionDDX46 is overexpressed in TE-1 cells. Targeted gene silencing of DDX46 inhibits cell growth, and induces cell apoptosis. DDX46 silencing probably by negative regulation of Akt/NF-κB signaling pathway, to play a role in inhibiting TE-1 cells growth and inducing apoptosis.
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.
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.
Objective To compare short-term quality of life and postoperative complications in esophageal squamous cell carcinoma patients with different routes reconstruction after McKeown esophagectomy. Methods The clinical data of 144 patients with esophageal squamous cell carcinoma who received McKeown esophagectomy in Shanghai Chest Hospital from January 2016 to October 2016 were retrospectively reviewed. Among them 93 patients accepted retrosternal approach (a RR group, 71 males and 22 females at an average age of 63.5±7.7 years) and 51 patients accepted posterior mediastinal approach (a PR group, 39 males and 12 females at an average age of 62.3±8.0 years). Short-term surgical outcomes were compared and a Quality of Life Questionnaire of Patients Underwent Esophagectomy 1.0 was performed at postoperative 1st and 3rd month. Results There was no difference in two groups in sex, age, Body Mass Index (BMI), and location and clinical stage of tumors (P>0.05). The neoadjuvant therapy was more performed in the RR group (16.1%vs. 5.9%, P=0.075). There were more robot-assisted esophagecctomy operations performed in the PR group (52.9% vs. 45.2%, P=0.020). No significant difference was noted in operation duration, intraoperative blood loss or length of ICU stay between the RR and PR groups (251.3±59.1 min vs. 253.1±27.7 min, P=0.862; 223.7±75.1 ml vs. 240.0±75.1 ml, P=0.276; 3.7±6.6 d vs. 2.3±2.1 d, P=0.139). The patients in the PR group had more lymph nodes dissected and shorter hospital stay (P<0.001). Rate of R1/2 resection was higher in the RR group (12.9%vs. 5.9%, P=0.187). No surgery-related mortality was observed in both groups. The anastomotic leak and the anastomotic stricture was higher in the RR group than that in the PR group (25.8% vs. 5.9%, P=0.003). No significant difference was found between the two groups in the quality of life at postoperative 1st and 3rd month. However, the quality of life at postoperative 3rd month significantly improved in both groups (P<0.001). Compared with the PR group, the dysphagia was more severe in the RR group at postoperative 1st month (3.3±1.5 vs. 2.6±1.1, P=0.007), while the reflux symptom was lighter at postoperative 3rd month (3.0±1.8 vs. 3.6±1.6, P=0.045). Conclusion The two different routes reconstruction after McKeown esophagectomy are both safe and feasible. The anterior mediastinal approach increases the risk of anastomotic leak, but with low incidence of reflux symptom.
Great progress has been made in immunotherapy for esophageal squamous cell carcinoma in recent years. However, for thoracic surgeons, immunotherapy is still a new thing and they lack enough experience. Therefore, this paper attempts to discuss some hot issues of immunotherapy, including the indications, side effects, clinical efficacy and evaluation of efficacy. The author hopes that this article will help and attract the attention of thoracic surgeons.
Objective To observe the growth of xenografted tumor in nude mice after DDX46 expression decreased, and to further study the role of DDX46 in the development and progression of esophageal squamous cell carcinoma. Methods DDX46-shRNA mediated RNAi was applied to silencing DDX46 in Eca-109 cells. Twenty-five female BALB/c nude mice were divided into 3 groups: an experiment group (DDX46-shRNA-LV, n=10), a control group (Control-LV, n=10) and a blank control group (Het-1A, n=5). The prepared Eca-109 cells of DDX46-shRNA-LV and Control-LV were subcutaneously injected into the right armpit of mice (4×106 cells per mouse), while Het-1A cells were subcutaneously injected into the bilateral armpits of mice (4×106 cells per side). Tumor growth was monitored twice a week on the 14th day after injection. Tumor volume was measured with calipers, in vivo imager to observe the fluorescence of each group. Further, western blotting analysis was used to detect the changes of apoptosis signaling molecules in xenografted tumor after DDX46 silence. Results The growth of xenografted tumor in nude mice was significantly slower in the DDX46-shRNA-LV group than that in the Control-LV group throughout the study period (P<0.001). Western blotting analysis showed that silencing DDX46 effectively suppressed the expression of DDX46, and upregulated the expression of cleaved Caspase-3 and cleaved PARP-1 in xenografted tumor (P<0.01). Conclusion DDX46 is involved in the development and progression of esophageal squamous cell carcinoma, and the silence of DDX46 expression can inhibit the growth of esophageal squamous cell carcinoma, which probably by positive regulation of apoptosis signaling pathway.
Esophageal squamous cell carcinoma can easily penetrate into the esophageal wall and invade adjacent organs due to the lack of serosa. Stage cT4b tumors involving organs adjacent to the aorta, vertebral body, trachea, or bronchus were considered unresectable. For unresectable esophageal squamous cell carcinoma, radical chemoradiotherapy or chemotherapy is recommended. However, the therapeutic effect is poor. With the advent of conversion surgery, surgical resection is feasible after induction therapy for patients with esophageal tumors that are initially unresectable due to adjacent organ invasion or distant metastasis. This article reviews the research on conversion surgery for unresectable esophageal squamous cell carcinoma in recent years in order to explore the clinical application prospects of conversion surgery.
ObjectiveTo construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. ResultsA total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.
ObjectiveTo investigate whether adjuvant therapy can bring survival benefits to patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant therapy plus esophagectomy. MethodsStudies were identified by searching databases including PubMed, EMbase, Web of Science, The Cochrane Library and CNKI from inception to November 2022 to collect studies which conformed to the objective of this study. Clinical outcomes including overall survival (OS) and recurrence-free survival (RFS) were extracted from eligible studies after screening. RevMan 5.4 and Stata 14.0 were used to perform the meta-analysis. ResultsA total of 9 studies were selected including 1 340 patients. Compared with the neoadjuvant therapy plus surgery (NS) group, the neoadjuvant therapy plus surgery+adjuvant therapy (NS+A) group had no significant benefit in the OS [HR=0.88, 95%CI (0.75, 1.02), P=0.09], but had remarkable benefit in the RFS [HR=0.75, 95%CI (0.58, 0.97), P=0.03]. Subgroup analysis by nodal status showed that adjuvant therapy could improve the RFS of patients with node-positive disease. Prolonged OS was observed in the patients with both positive and negative nodes but not in the patients with only positive nodes. In terms of the subgroup analysis by prescription, it revealed that triple agents exhibited advantages in improving RFS but not OS. However, dual agents did not bring additional survival benefits to the NS+A group compared with the NS group. Subgroup analysis by adjuvant therapy indicated that neither postoperative chemoradiotherapy nor chemotherapy improved OS, whereas postoperative chemoradiation elongated RFS. ConclusionAdjuvant therapy can improve the prognosis of patients with ESCC after neoadjuvant therapy followed by esophagectomy.