Comprehensive Analysis Revealed that CDKN2A is a Biomarker for Immune Infiltrates in Multiple Cancers

被引:58
作者
Chen, Zheng [1 ,2 ]
Guo, Yingjie [1 ,3 ]
Zhao, Da [1 ,2 ]
Zou, Quan [1 ]
Yu, Fusheng [4 ]
Zhang, Lijun [2 ]
Xu, Lei [3 ]
机构
[1] Univ Elect Sci & Technol China, Inst Fundamental & Frontier Sci, Chengdu, Peoples R China
[2] Shenzhen Polytech, Sch Appl Chem & Biol Technol, Shenzhen, Peoples R China
[3] Shenzhen Polytech, Sch Elect & Commun Engn, Shenzhen, Peoples R China
[4] Gen Hosp, Beidahuang Ind Grp, Harbin, Peoples R China
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
基金
中国国家自然科学基金;
关键词
CDKN2A; TMB; MSI; immune infiltrates; pan-cancer; TUMOR-SUPPRESSOR GENE; PROMOTER METHYLATION; MELANOMA; P16(INK4A); EXPRESSION; P16; OVEREXPRESSION; SUSCEPTIBILITY; PROGRESSION; SENESCENCE;
D O I
10.3389/fcell.2021.808208
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The CDKN2A (cyclin dependent kinase inhibitor 2A/multiple tumor suppressor 1) gene, also known as the P16 gene, encodes multiple tumor suppressor 1 (MTS1), which belongs to the INK4 family. In tumor tissue, CDKN2A has a high expression level compared with normal tissue and reflects prognosis in tumor patients. Our research targeted the analysis of CDKN2A expression in 33 tumors and clinical parameters, patient prognosis and tumor immunity roles. The CDKN2A expression level was significantly correlated with the tumor mutation burden (TMB) in 10 tumors, and the expression of CDKN2A was also correlated with MSI (microsatellite instability) in 10 tumors. CDKN2A expression was associated with infiltrating lymphocyte (TIL) levels in 22 pancancers, thus suggesting that CDKN2A expression is associated with tumor immunity. Enrichment analysis indicated that CDKN2A expression was involved in natural killer cell-mediated cytotoxicity pathways, antigen processing and presentation, olfactory transduction pathways, and regulation of the autophagy pathway in multiple cancers. CDKN2A was significantly associated with several immune cell infiltrates in pantumors. CDKN2A may serve as a promising prognostic biomarker and is associated with immune infiltrates across cancers.
引用
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页数:13
相关论文
共 49 条
[1]   The p16 (CDKN2a/INK4a) tumor-suppressor gene in head and neck squamous cell carcinoma: A promoter methylation and protein expression study in 100 cases [J].
Ai, LB ;
Stephenson, KK ;
Ling, WH ;
Zuo, CL ;
Mukunyadzi, P ;
Suen, JY ;
Hanna, E ;
Fan, CY .
MODERN PATHOLOGY, 2003, 16 (09) :944-950
[2]   Genetics of melanoma progression: the rise and fall of cell senescence [J].
Bennett, Dorothy C. .
PIGMENT CELL & MELANOMA RESEARCH, 2016, 29 (02) :122-140
[3]   p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells [J].
Cen, Ling ;
Carlson, Brett L. ;
Schroeder, Mark A. ;
Ostrem, Jamie L. ;
Kitange, Gaspar J. ;
Mladek, Ann C. ;
Fink, Stephanie R. ;
Decker, Paul A. ;
Wu, Wenting ;
Kim, Jung-Sik ;
Waldman, Todd ;
Jenkins, Robert B. ;
Sarkaria, Jann N. .
NEURO-ONCOLOGY, 2012, 14 (07) :870-881
[4]   Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic [J].
Chan, T. A. ;
Yarchoan, M. ;
Jaffee, E. ;
Swanton, C. ;
Quezada, S. A. ;
Stenzinger, A. ;
Peters, S. .
ANNALS OF ONCOLOGY, 2019, 30 (01) :44-56
[5]   Cooperativity of Oncogenic K-Ras and Downregulated p16/INK4A in Human Pancreatic Tumorigenesis (Publication with Expression of Concern. See vol. 14, 2019) [J].
Chang, Zhe ;
Ju, Huaiqiang ;
Ling, Jianhua ;
Zhuang, Zhuonan ;
Li, Zhongkui ;
Wang, Huamin ;
Fleming, Jason B. ;
Freeman, James W. ;
Yu, Dihua ;
Huang, Peng ;
Chiao, Paul J. .
PLOS ONE, 2014, 9 (07)
[6]   DincRNA: a comprehensive web-based bioinformatics toolkit for exploring disease associations and ncRNA function [J].
Cheng, Liang ;
Hu, Yang ;
Sun, Jie ;
Zhou, Meng ;
Jiang, Qinghua .
BIOINFORMATICS, 2018, 34 (11) :1953-1956
[7]   IntNetLncSim: an integrative network analysis method to infer human lncRNA functional similarity [J].
Cheng, Liang ;
Shi, Hongbo ;
Wang, Zhenzhen ;
Hu, Yang ;
Yang, Haixiu ;
Zhou, Chen ;
Sun, Jie ;
Zhou, Meng .
ONCOTARGET, 2016, 7 (30) :47864-47874
[8]   Loss of Wild-Type CDKN2A Is an Early Event in the Development of Melanoma in FAMMM Syndrome [J].
Christodoulou, Eirini ;
Nell, Rogier J. ;
Verdijk, Rob M. ;
Gruis, Nelleke A. ;
van der Velden, Pieter A. ;
van Doorn, Remco .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2020, 140 (11) :2298-+
[9]  
Christopher SA, 2002, CANCER RES, V62, P6639
[10]   Apoptosis and cancer: the genesis of a research field [J].
Cotter, Thomas G. .
NATURE REVIEWS CANCER, 2009, 9 (07) :501-507