Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma

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.