Prognostic, clinicopathological, and immune correlation of NLRP3 promoter methylation in kidney renal clear cell carcinoma.
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ABSTRACT:
SUBMITTER: Long Q
PROVIDER: S-EPMC8530444 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Prognostic, clinicopathological, and immune correlation of NLRP3 promoter methylation in kidney renal clear cell carcinoma.
Long Qian Q He Liru L Peng Jin J Meng Qi Q Zhang Changlin C Chen Miao M Wang Xiaonan X Zhu Wancui W Zheng Fufu F Dong Pei P Deng Wuguo W
Clinical and translational medicine 20211001 10
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Project description:IntroductionJanus kinase 3 (JAK3) is a well-established oncogene in clear cell renal cell carcinoma (ccRCC). The methylation status of oncogene promoters has emerged as biomarkers for cancer diagnosis and prognosis.ObjectiveThis study aims to investigate the biological and clinical significance of JAK3 promoter methylation in ccRCC.MethodsWe analyzed the relationship of JAK3 promoter methylation with its mRNA expression, overall survival, and immune cell infiltration in a cohort obtained from The Cancer Genome Atlas (TCGA), which was further validated by another independent cohort. We further validated correlations of JAK3 promoter methylation with JAK3 expression, overall survival, and immune cell infiltration in an independent ccRCC cohort (Sun Yat-sen University Cancer Center (SYSUCC) cohort) by methods of immunohistochemistry (IHC) and pyrosequencing.ResultsWe found JAK3 promoter was significantly hypomethylated in tumor tissues compared to normal adjacent tissues in ccRCC, and JAK3 promoter hypomethylation was strongly correlated with high JAK3 mRNA expression in all three ccRCC cohorts we examined. JAK3 promoter hypomethylation predicted advanced clinicopathological characteristics and shorter overall survival (TCGA cohort and SYSUCC cohort). Furthermore, we found that JAK3 promoter methylation was significantly associated with immune cell infiltration and expression of immune checkpoint molecules (TCGA cohort and CPTAC cohort). Finally, our SYSUCC cohort validated that JAK3 promoter methylation was correlated with CD4+ and CD8+ T cell infiltration in ccRCC tumor tissues.ConclusionOur data demonstrated that the crucial role of JAK3 promoter methylation in its expression regulation and tumor microenvironment. JAK3 promoter methylation and expression are associated with clinicopathological characteristics, overall survival, and immune cell infiltration in ccRCC. We propose a rationale for further validation of JAK3 promoter methylation as a molecular biomarker for predicting responses to immune checkpoint inhibitors in ccRCC.
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