Prognostic value of JAK3 promoter methylation and mRNA expression in clear cell renal cell carcinoma.
Prognostic value of JAK3 promoter methylation and mRNA expression in clear cell renal cell carcinoma.
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DOI：
10.1016/j.jare.2021.11.016
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发表时间：
2022-09
影响因子：
10.7
通讯作者：
Deng, Wuguo
中科院分区：
文献类型：
--
作者：
Long, Qian;Huang, Chunyu;Huang, Jinsheng;Meng, Qi;Cheng, Yanjun;Li, Yilin;He, Liru;Chen, Miao;Zhang, Changlin;Wang, Xiaonan;Zhu, Wancui;Peng, Jin;Shi, Dingbo;Zheng, Fufu;Dong, Pei;Deng, Wuguo
关键词：
JAK3 promoter methylation was correlated with JAK3 expression in ccRCC. JAK3 promoter methylation was associated with clinicopathological characteristics in ccRCC. JAK3 promoter methylation was associated with overall survival in ccRCC. JAK3 promoter methylation was correlated with immune cell infiltration in ccRCC. JAK3 promoter methylation was correlated with the expression of immune checkpoint molecules in ccRCC. JAK3 promoter methylation was a potential biomarker for predicting responses to immune checkpoint inhibitors in ccRCC. Janus 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. This study aims to investigate the biological and clinical significance of JAK3 promoter methylation in ccRCC. We 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. We 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. Our 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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DOI：
10.1038/s41571-020-00455-z
发表时间：
2021-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Braun DA;Bakouny Z;Hirsch L;Flippot R;Van Allen EM;Wu CJ;Choueiri TK
通讯作者：
Choueiri TK
影响因子：
3.8
作者：
Lingohr, Philipp;Dohmen, Jonas;Dietrich, Dimo
通讯作者：
Dietrich, Dimo
DOI：
10.1016/s0140-6736(16)00561-4
发表时间：
2016-05-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Rosenberg JE;Hoffman-Censits J;Powles T;van der Heijden MS;Balar AV;Necchi A;Dawson N;O'Donnell PH;Balmanoukian A;Loriot Y;Srinivas S;Retz MM;Grivas P;Joseph RW;Galsky MD;Fleming MT;Petrylak DP;Perez-Gracia JL;Burris HA;Castellano D;Canil C;Bellmunt J;Bajorin D;Nickles D;Bourgon R;Frampton GM;Cui N;Mariathasan S;Abidoye O;Fine GD;Dreicer R
通讯作者：
Dreicer R
影响因子：
5.6
作者：
Liang, Feiguo;Liang, Hao;Huang, Peiyuan
通讯作者：
Huang, Peiyuan
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T