Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma.
Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma.
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CLDN8 在透明细胞肾细胞癌患者中的预后价值和潜在生物学功能
DOI：
10.2147/ott.s266846
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发表时间：
2020
影响因子：
4
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Zhu Z;Xu C;Lin L;Lv T;Cai T;Lin J
目的肾透明细胞癌（Clear cell renal cell carcinoma，ccRCC）是世界上最常见的恶性肿瘤之一，发病率高，预后差。目前，没有生物标志物可以准确指导ccRCC的预后评估和治疗策略。claudin-8（CLDN 8）是ccRCC中紧密连接的关键组分，其预后价值和潜在生物学功能尚不清楚。方法测序数据来源于The Cancer Genome Atlas、International Cancer Genome Consortium和Gene Expression Omnibus数据库。使用R软件包探索CLDN 8 mRNA表达水平并分析差异表达基因。在临床标本和细胞系中验证结果，并进行生物信息学分析以探索CLDN 8的潜在生物学功能。最后，使用786- 0 ccRCC细胞系进行功能分析。结果ccRCC组织中CLDN 8 mRNA和蛋白表达水平均低于正常对照组。Kaplan-Meier分析显示CLDN 8低表达水平与总生存率相关，而单因素和多因素考克斯回归表明CLDN 8可作为ccRCC患者的独立预后因素。生物信息学和蛋白质印迹分析显示，CLDN 8通过上皮-间充质转化和AKT途径抑制786- 0 ccRCC细胞的增殖、迁移和侵袭。结论CLDN 8通过EMT和AKT途径抑制786-O的增殖、迁移和侵袭，可作为肾细胞癌的独立预后因子。
Purpose Clear cell renal cell carcinoma (ccRCC) is among the most common malignant tumors worldwide, with a high incidence rate and poor prognosis. Currently, there are no biomarkers that can accurately guide prognostic evaluation and therapeutic strategy for ccRCC. The prognostic value and potential biological function of claudin-8 (CLDN8), a critical component of tight junctions in ccRCC, remain unclear. Methods Sequencing data were obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R packages were used to explore CLDN8 mRNA expression levels and analyze differentially expressed genes. Results were validated in clinical specimens and cell lines, and bioinformatics analyses were conducted to explore the potential biological functions of CLDN8. Finally, functional analyses were carried out using 786–O ccRCC cell line. Results Both CLDN8 mRNA and protein expression levels were significantly lower in ccRCC compared with the normal control tissues. Kaplan–Meier analyses showed that low CLDN8 expression levels were associated with the poor overall survival, while univariate and multivariate Cox regression indicated that CLDN8 could serve as an independent prognostic factor in patient with ccRCC. Bioinformatic and Western blot analyses showed that CLDN8 suppressed proliferation, migration, and invasion of 786–O ccRCC cells through the epithelial–mesenchymal transition and AKT pathways. Conclusion CLDN8 could serve as an independent prognostic factor in ccRCC, in which it suppresses 786–O proliferation, migration, and invasion through EMT and AKT pathways.