ObjectiveTo investigate the prognostic factors of primary gastric squamous cell carcinoma (SCC) and develop a nomogram for predicting the survival of gastric SCC.MethodsData of 199 cases of primary gastric SCC from 2004 to 2015 were collected in the National Cancer Institute SEER database by SEER Stat 8.3.5 software. X-tile software was used to determine the best cut-off value of the age, SPSS 25.0 software was used to analyze the prognostic factors of gastric SCC and draw a Kaplan-Meier curve, and then the Cox proportional hazard regression model analysis was performed to obtain independent prognostic factors of gastric SCC. We used R studio software to visualize the model and draw a nomogram. C-index was used to evaluate the prediction effect of the nomogram. Bootstrap analyses with 1 000 resamples were applied to complete the internal verification of the nomogram.ResultsAmong the 199 patients, survival rates for 1-, 3-, and 5-year were 40.7%, 22.4%, and 15.4%, respectively. Age (χ2=6.886, P=0.009), primary site (χ2=14.918, P=0.037), race (χ2=7.668, P=0.022), surgery (χ2=16.523, P<0.001), histologic type (χ2=9.372, P=0.009), T stage (χ2=11.639, P=0.009), and M stage (χ2=31.091, P<0.001) had a significant correlation with survival time of patients. The results of the Cox proportional hazard regression model showed that, age [HR=1.831, 95%CI was (1.289, 2.601)], primary site [HR=1.105, 95%CI was (1.019, 1.199)], M stage [HR=2.222, 95%CI was (1.552, 3.179)], and surgery [HR=0.561, 95%CI was (0.377, 0.835)] were independent prognostic factors affecting the survival of gastric SCC. Four independent prognostic factors contributed to constructing a nomogram with a C-index of 0.700.ConclusionIn this research, a reliable predictive model is constructed and drawn into a nomogram, which can be used for clinical reference.
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.
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 evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.
Objective To investigate the prognostic value of preoperative plasma fibrinogen (FIB) combined with lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of patients with esophageal squamous cell carcinoma. Methods A retrospective analysis was conducted on patients who underwent esophagectomy in our hospital from January 2015 to December 2018. Based on the cut-off values of preoperative FIB and LMR, The F-LMR scoring system was constructed, and patients were divided into three groups. Kaplan-Meier analysis was used to assess 5-year overall survival and 5-year progression free survival, and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Results Finally 260 patients were collected, including 237 males and 23 females, with a median age of 64 years (ranging from 59 to 70 years). The 5-year OS rates for patients with F-LMR score of 0, 1, and 2 were 24.44%, 51.69%, and 67.31%, respectively, and the 5-year PFS rates were 15.56%, 42.37%, and 57.62%, respectively. Lower preoperative F-LMR scores were associated with worse prognosis. Multivariate analysis showed that deeper tumor invasion, presence of lymph node metastasis, larger tumor maximum diameter, and lower preoperative F-LMR score were independent prognostic factors for OS. Conclusion The F-LMR score system based on the preoperative FIB and LMR can serve as an effective tool for predicting the prognosis of patients with esophageal squamous cell carcinoma.
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 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.
ObjectiveTo establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis.MethodsRNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models.ResultsThe risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC.ConclusionThe ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.
ObjectiveTo systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis.MethodsThe literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis.Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.0001).ConclusionPD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.
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.