期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.798319
关键词
protein kinase C; pan-cancer study; biomarker; tumors immune landscape; immunotherapy
资金
- Recruitment Program of Overseas High-Level Young Talents, National Natural Science Foundation, Innovative and Entrepreneurial Team [(2018) 2015]
- Science and Technology Grant of Jiangsu Province [BE2019758]
- Six Talent Peaks Project of Jiangsu Province [TD-SWYY-007]
- Science and Technology Bureau of Wenzhou
- Beijing Xisike Clinical Oncology Research Foundation [Y-HS 2019-35, YBMS2019-071]
- Nanjing Medical University
- Yijishan Hospital of Wannan Medical College
- Anhui Provincial Central Government's Special Program for Local Science and Technology Development [YDZX20183400004899]
- University Academic (Professional) Top Talents Academic Funding Project [gxbjZD17]
This study investigates the correlation between PKC genes and tumor immunity, as well as their potential as predictive biomarkers for tumor immunity and immunotherapeutic response. The results suggest that PKC isoenzymes can serve as robust biomarkers for the tumor immune status and can be used as predictors for the response to immunotherapies.
The protein kinase C (PKC) family has been described with its role in some cancers, either as a promoter or suppressor. PKC signaling also regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha (PPARalpha). However, the role of different PKC enzymes in tumor immunity remains poorly defined. This study aims to investigate the correlation between PKC genes and tumor immunity, in addition to studying the probability of their use as predictive biomarkers for tumor immunity and immunotherapeutic response. The ssGSEA and the ESTIMATE methods were used to assess 28 tumor-infiltrating lymphocytes (TILs) and the immune component of each cancer, then correlated with PKC levels. Prediction of PKC levels-dependent immunotherapeutic response was based on human leukocytic antigen (HLA) gene enrichment scores and programmed cell death 1 ligand (PD-L1) expression. Univariate and multivariate Cox analysis was performed to evaluate the prognostic role of PKC genes in cancers. Methylation level and CNAs could drive the expression levels of some PKC members, especially PRKCI, whose CNGs are predicted to elevate their level in many cancer types. The most crucial finding in this study was that PKC isoenzymes are robust biomarkers for the tumor immune status, PRKCB, PRKCH, and PRKCQ as stimulators, while PRKCI and PRKCZ as inhibitors in most cancers. Also, PKC family gene levels can be used as predictors for the response to immunotherapies, especially HLAs dependent and PD-L1 blockade-dependent ones. In addition to its prognostic function, all PKC family enzymes are promising tumor immunity biomarkers and can help select suitable immune therapy in different cancers.
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