GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma

Huang,Hongshuang; Chen,Ru; Deng,Xinxi; Wang,Jie; Chen,Jianhui

doi:10.3892/ol.2024.14219

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma

Authors:
- Hongshuang Huang
- Ru Chen
- Xinxi Deng
- Jie Wang
- Jianhui Chen
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Affiliations: Department of Urology, The Affiliated Hospital of Putian University, Putian, Fujian 351100, P.R. China, Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China, Department of Urology, Jiujiang No. 1 People's Hospital, Jiujiang, Jiangxi 332000, P.R. China, Department of Ultrasound, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Urology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350000, P.R. China
Published online on: January 5, 2024 https://doi.org/10.3892/ol.2024.14219
Article Number: 85
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression‑free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

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