OncoTargets and Therapy (Sep 2020)
Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma
Abstract
Zhenpeng Zhu,1– 3 Chunru Xu,1– 3 Lanruo Lin,4 Tongde Lv,1– 3 Tianyu Cai,1– 3 Jian Lin1– 3 1Department of Urology, Peking University First Hospital, Beijing 100034, People’s Republic of China; 2Institute of Urology, Peking University, Beijing 100034, People’s Republic of China; 3Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing 100034, People’s Republic of China; 4College of Basic Medical Science, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Jian LinDepartment of Urology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of ChinaTel +86 13801358465Fax +86 10 66551211Email [email protected]: 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.Keywords: CLDN8, clear cell renal cell carcinoma, biomarker, prognosis, potential biological functions
