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Abstract：
Several studies have reported the role of CLCN4 in tumor progression. However, its mechanism remains to be thoroughly studied. The objective of this study was to explore the potential pathogenic role of CLCN4 in endometrial carcinoma (UCEC) with a better understanding of the pathological mechanisms involved. The potential roles of CLCN4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), the expression difference, mutation, survival, pathological stage, Immunity subtypes, Immune infiltration, tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) related to CLCN4 were analyzed. Then, the expression, prognosis, mutation, and functional enrichment of CLCN4 in UCEC were analyzed. Immunohistochemical experiment was used to verify the expression of CLCN4 in endometrial cancer tissues and normal tissues. In vitro, we knocked down of CLCN4 in HEC-1-A cells and performed CCK8, WB, RT-PCR, wound-healing, transwell assays to further validation of the molecular function. Results revealed that high expression of CLCN4 was observed in 20 cancer types of TCGA. CLCN4 expression correlates with poor survival in MESO, BLCA, THCA, especially UCEC tumors. CLCN4 expression was significantly associated with CD4+ T-cell infiltration, especially CD4+ Th1-cell. Immunohistochemical experiment reveals that CLCN4 is high expressed in endometrial tumors, in vitro experiment reveals that knockdown of CLCN4 inhibits the cells proliferation, migration and invasion. Our study is the first to offer a comprehensive understanding of the oncogenic roles of CLCN4 on different tumors. CLCN4 may become a potential biomarker in UCEC.
摘要：
一些研究报道了CLCN4在肿瘤进展中的作用。然而,其机制仍有待深入研究。这项研究的目的是探讨CLCN4在子宫内膜癌（UCEC）中的潜在致病作用，并更好地了解其中的病理机制。基于癌症基因组图谱(TCGA)探讨了CLCN4在不同肿瘤中的潜在作用。表达差异，突变,生存,病理阶段,免疫亚型,免疫浸润,肿瘤微环境（TME），肿瘤突变负荷（TMB），微卫星不稳定性（MSI），分析与CLCN4相关的错配修复(MMR)。然后，表达式，预后,突变,并对CLCN4在UCEC中的功能富集进行了分析。免疫组化实验验证CLCN4在子宫内膜癌组织和正常组织中的表达。体外，我们在HEC-1-A细胞中敲除CLCN4，并进行CCK8，WB，RT-PCR,伤口愈合,transwell分析以进一步验证分子功能。结果显示在20种癌症类型的TCGA中观察到CLCN4的高表达。CLCN4表达与MESO中的低生存率相关，BLCA,THCA,尤其是UCEC肿瘤。CLCN4表达与CD4+T细胞浸润显著相关,特别是CD4+Th1细胞。免疫组织化学实验显示CLCN4在子宫内膜肿瘤中高表达,体外实验表明，敲低CLCN4抑制细胞增殖，移民和入侵。我们的研究首次全面了解CLCN4对不同肿瘤的致癌作用。CLCN4可能成为UCEC的潜在生物标志物。
