J Cancer 2020; 11(24):7348-7356. doi:10.7150/jca.48970

Research Paper

Differential expression of epithelial sodium channels in human RCC associated with the prognosis and tumor stage: Evidence from integrate analysis

Shangfan Liao1, Huaibin Huang1, Fabiao Zhang1, Dongming Lu1, Shuchao Ye1, Luoping Zheng1, Yingming Sun2, Yongyang Wu1✉

1. Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming365100, Fujian, PR. China.
2. Department of Medical and Radiation Oncology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming365100, Fujian, PR. China.

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Citation:
Liao S, Huang H, Zhang F, Lu D, Ye S, Zheng L, Sun Y, Wu Y. Differential expression of epithelial sodium channels in human RCC associated with the prognosis and tumor stage: Evidence from integrate analysis. J Cancer 2020; 11(24):7348-7356. doi:10.7150/jca.48970. Available from https://www.jcancer.org/v11p7348.htm

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Abstract

Background: Epithelial sodium channels are disputed in renal cell carcinoma, but its functions and effects on clinical outcomes are not well understood.

Materials and Methods: IHC and PT-PCR were used to detect ENaCα, β, γ, AVPR2, AQP2, and MR expression in the primary tumor and peritumoral tissues. GEPIA online tool was used to analyze the relationship between epithelial sodium channels and clinical-pathological characteristics. Tumor IMmune Estimation Resource online tool was used to investigate the immune profile relevant to epithelial sodium channels expression.

Results: Quantitative RT-PCR analysis revealed that ENaCα, β, γ, AQP2, and AVPR2 mRNA were decreased in the RCC, but there was no difference in MR mRNA expression between kidney and RCC (p=0.238). The IHC analyses showed that the intensely positive staining of ENaCα, β, γ, AVPR2, and AQP in the renal tubular and the attenuated in the RCCs. MR displayed moderate staining in both RCC and normal tissue. With the promotion of staging, the expression of AQP2, AVPR2, and MR reduced gradually and predicted a better prognosis. Although ENaCα, β, and γ were unable to associate with staging, we still observed a high expression of ENaCβ and γ displayed a poorer prognosis of RCC.

Conclusions: ENaCs shows an oncogene profile in RCC, drugs targeting epithelial sodium channel should be a possible therapeutic way to treat RCC. AVPR2 and MR exhibit an encouraging immunomodulatory function; patients with low expression of AVPR2 and MR may obtain more benefit from immunotherapy.

Keywords: Renal Cell Carcinoma, Epithelial Sodium Channel Proteins, Prognosis, Integrate Analysis