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Background: Thrombospondin type 1 domain-containing 7A (THSD7A) was reported to play a procancer role in esophageal squamous cell carcinoma (ESCC). The aim of the study was to screen the downstream functional genes of THSD7A and explore their functions in ESCC, based on the reported research into THSD7A function and on gene microarrays.Methods: We adopted quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Celigo high-content screening (HCS) technology to screen the downstream genes of THSD7A. The expression level of target genes was examined by PCR, western blot, and immunohistochemistry (IHC). The effects of these target genes on ESCC malignant biological behavior were performed in vivo and in vitro. The Kaplan-Meier (K-M) survival analysis and Cox regression were used to analyze the prognostic significance of target genes in ESCC patients. Experiments in the literature on liver cancer (LC) were repeated to verify the functions of these genes in different tumors. We further explored the cancer-promoting mechanism of target genes in ESCC by sequencing of the genes' exons.Results: Scavenger receptor class A member 5 (SCARA5) was proved to be the downstream driving gene of THSD7A. SCARA5 promoted cell proliferation and migration but inhibited apoptosis in ESCC. IHC results confirmed that SCARA5 expression in ESCC exceeded that in normal tissues. The K-M survival analysis indicated that SCARA5 expression quantity was not related to prognosis, but tumor volume and T classification were both the independent prognostic factors. Repetition of experiments in LC in the literature confirmed that SCARA5 had exactly opposite functions in EC and LC.Conclusion: SCARA5 was related to the development and occurrence of ESCC. Our findings suggested that it was a potentially diagnostic individualized therapeutic target for ESCC in the future and that its application could possibly be combined with that of upstream THSD7A gene. [ABSTRACT FROM AUTHOR]

Abstract: Background: To demonstrate the effect of an inherited predisposition in familial Esophageal Squamous Cell Carcinoma (ESCC) as opposed to the sporadic cancer form. Methods: Differences in age of onset, prevalence rates of double primary ESCC, and post-operative survival rates between ESCC cases with (N = 476) and without (N = 1226)a family history of upper gastrointestinal cancer (FHUGIC, defined as having one or more first- or second-degree relatives with cancer of the esophagus or gastric cardia) were analyzed. Results: Overall, familial ESCC cases show a significantly earlier onset age (51.9 ± 8.2 versus 53.4 ± 8.0, Pt -test = .000), a significantly higher prevalence rate of double primary ESCC (2.73% Versus 1.22%, adjusted with TNM: X MH 2 = 4.029, P = .045), and a worse prognosis than the sporadic cases (P wald = .049). In subgroup analyses, the familial cases showed earlier onset and poor survival at most subgroups as opposed to the sporadic cases, and the difference was greater in early-stage rather than in late-stage groups (Pt-test for difference in onset age in Tis,1N0M0, T2,3N0M0, and T2,3,4N1M0 were .002, .006, and .081 respectively; and P wald for difference in survival in Tis,1N0M0, T2,3N0M0, and in T2,3,4N1M0 were .010, .180, and .520 respectively). Conclusion: These findings suggest the existence of familial as opposed to the sporadic ESCC. By the theory of “two-hit” origin of cancer, these findings also suggest that the “first hit”, a genetic predisposition, is inherited in familial ESCC. [Copyright &y& Elsevier]

The aim of the present study was to investigate the association between tumor protein 53 (TP53) gene deletion and protein expression and clinical features in esophageal squamous cell carcinoma (ESCC), and to evaluate the predictive value of these two characteristics in the prognosis of ESCC. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were performed to detect the expression of p53 protein and gene deletion in ESCC tissue samples from different ethnic groups in Xinjiang, in order to analyze their association with clinicopathological characteristics and patient prognosis, as well as the sensitivity and specificity of the two methods. In addition, the results were further validated by tissue microarray from a different region. The positive rate of p53 protein expression was 54.5% (201/369) in the multi-ethnic group, and was significantly different between sex (P=0.026) and between tumor differentiation groups (P=0.032). FISH demonstrated that the TP53 gene deletion rate was 31.8% (68/214), which was significantly different between different tumor differentiation (P=0.002), lymph node metastasis (P=0.005) and vascular invasion (P<0.001) groups. The survival rate of patients with TP53 gene deletion was significantly lower than those without TP53 gene deletion (P<0.05). The positive rate of p53 protein expression in the tissue microarray was 58.1% (68/117), which was significantly different between the depth of invasion groups (P=0.011). The TP53 gene deletion rate was 47.9% (56/117), which significantly differed according to lymph node metastasis (P=0.003) and TNM stage (P=0.01). In addition, the total concordance rates of the two methods were 60.3 and 64.1%, respectively. There were also significant differences in the positive rate of TP53 gene deletion and protein expression in different stages of ESCC (P<0.05), which increased gradually with the progression of ESCC. The deletion of the TP53 gene in esophageal cancer was associated with poor prognosis and may be an important biomarker for evaluating the prognosis of patients with ESCC. The combination of FISH and IHC methods could significantly improve the detection rate of TP53 gene abnormalities and the accuracy of prognostic assessment of ESCC. [ABSTRACT FROM AUTHOR]