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. 2023 Jul;45(7):855-866.
doi: 10.1007/s13258-023-01376-8. Epub 2023 May 3.

Inactivation of epithelial sodium ion channel molecules serves as effective diagnostic biomarkers in clear cell renal cell carcinoma

Qian Zheng #  1   2 , Yifang Wang #  2 , Ran Zhao #  1   2 , Peipei Han  2 , Jun Zhao  2 , Limei Li  2 , Xiaohui Zhou  1   2 , Ping Li  2 , Yingxi Mo  2 , Xinli Pan  3 , Wenqi Luo  4 , Xiaoying Zhou  5   6
Affiliations

Inactivation of epithelial sodium ion channel molecules serves as effective diagnostic biomarkers in clear cell renal cell carcinoma

Qian Zheng et al. Genes Genomics. 2023 Jul.

Abstract

Background: Non-voltage-gated sodium channel, also known as the epithelial sodium channel (ENaC), formed by heteromeric complexes consisting of SCNN1A, SCNN1B, and SCNN1G, is responsible for maintaining sodium ion and body fluid homeostasis in epithelial cells. However, no systematic study of SCNN1 family members has been conducted in renal clear cell carcinoma (ccRCC) to date.

Objective: To investigate the abnormal expression of SCNN1 family in ccRCC and its potential correlation with clinical parameters.

Methods: The transcription and protein expression levels of SCNN1 family members in ccRCC were analyzed based on the TCGA database, and were confirmed by quantitative RT-PCR and immunohistochemical staining assays, respectively. The area under curve (AUC) was used to evaluate the diagnostic value of SCNN1 family members for ccRCC patients.

Results: The mRNA and protein expression of SCNN1 family members was significantly downregulated in ccRCC compared with normal kidney tissues, which might be due to DNA hypermethylation in the promoter region. It is worth noting that the AUC of SCNN1A, SCNN1B, and SCNN1G were 0.965, 0.979, and 0.988 based on the TCGA database (p < 0.0001), respectively. The diagnostic value was even higher when combing these three members together (AUC = 0.997, p < 0.0001). Intriguingly, the mRNA level of SCNN1A was significantly lower in females compared with males, while SCNN1B and SCNN1G were increased with the progression of ccRCC and remarkably associated with a worse outcome for patients.

Conclusion: The aberrantly decrease of SCNN1 family members might serve as valuable biomarkers for the diagnosis of ccRCC.

Keywords: Clear cell renal cell carcinoma; Diagnostic biomarker; Epithelial sodium channel; Hypermethylation.

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