基于生物信息学分析铜死亡相关基因CDKN2A在肾上腺皮质癌中的作用机制  

Bioinformatics analysis of the functional mechanism of the cuprotosis-related gene CDKN2A in adrenocortical carcinoma

作　　者：闫泽晨[1] 刘统虎 李志愿 任翼麟 朱聪聪 栾永坤 王宇[3] 杨肖杰 高宇奎 Yan Zechen;Liu Tonghu;Li Zhiyuan;Ren Yilin;Zhu Congong;Luan Yongkun;Wang Yu;Yang Xiaojie;Gao Yukui(Department of Urology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450001,China;Department of Oncology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450001,China;Henan Institute of Medical and Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China;Department of Urology,the First Affiliated Hospital of Wannan Medical College,Yijishan Hospital,Wuhu 241001,China)

机构地区：[1]郑州大学第一附属医院泌尿外科,郑州450001 [2]郑州大学第一附属医院肿瘤科,郑州450001 [3]郑州大学华大基因学院,郑州450001 [4]皖南医学院第一附属医院泌尿外科,241001

出　　处：《中华实验外科杂志》2024年第2期279-285,共7页Chinese Journal of Experimental Surgery

基　　金：河南省医学科技攻关项目(SBGJ202002032)。

摘　　要：目的通过生物信息学分析铜死亡相关基因在肾上腺皮质癌(ACC)中的相关作用机制。方法联合肿瘤基因图谱(TCGA)以及GTEx数据库(肾上腺皮质癌:77例, 对照:128例)筛选出目标基因(CDKN2A)。通过临床相关性分析、生存分析、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析从而探讨目标基因的相关功能以及在ACC中对预后的影响。通过免疫相关分析、药物敏感性分析研究目标基因与ACC中免疫细胞浸润以及药物敏感性之间的关系。通过卡方检验判断CDKN2A在不同临床因素分型中的表达差异性、通过R软件包的"survival"方法进行生存相关分析, 探讨CDKN2A的预后价值, 通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析探讨CDKN2A的相关功能。通过免疫相关分析、药物敏感性分析研究目标基因与ACC中免疫细胞浸润以及药物敏感性之间的关系。结果 CDKN2A在皮质癌中的表达量高于对照组(|log2FC|>2, P<0.05), CDKN2A的表达与ACC患者临床分级(χ^(2)=12.63, P<0.01)以及T分期(χ^(2)=14.17, P<0.01)相关。生存分析结果显示, CDKN2A表达量高的ACC患者预后较表达量低的患者差(风险比1.818, 95%可信区间:1.295~2.552, P<0.05)。富集分析的结果显示CDKN2A与肿瘤的发生发展相关。CDKN2A在ACC中与多种抗肿瘤药物的敏感性以及免疫检查点IDO1密切相关(cor=0.3, P<0.05), 且与ACC的肿瘤突变负荷呈正相关(R=0.49, P<0.01)。结论铜死亡相关基因CDKN2A与ACC预后、侵袭、免疫微环境以及药物敏感性密切相关。Objective To investigate the action mechanism of cuprotosis-related genes in adrenocortical carcinoma(ACC)through bioinformatics analysis.Methods We combined data from the TCGA and GTEx databases(adrenocortical carcinoma:77 cases;control:128 cases)to identify target genes(CDKN2A).The differential expression of CDKN2A in different clinical subtypes was assessed using the chi-square test.Survival analysis was conducted using the"survival"package in R to investigate the prognostic value of CDKN2A.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to explore the functional relevance of CDKN2A.Immunological and drug sensitivity analyses were conducted to study the relationship between the target gene and immune cell infiltration as well as drug sensitivity in ACC.Results CDKN2A was upregulated in ACC compared to the control group(|log2FC|>2,P<0.05).The expression of CDKN2A was associated with clinical staging(χ^(2)=12.63,P<0.01)and T stage(χ^(2)=14.17,P<0.01)in ACC patients.Survival analysis revealed that ACC patients with high CDKN2A expression had worse prognosis than to those with low expression(hazard ratio 1.818,95%confidence interval:1.295-2.552,P<0.05).Enrichment analysis indicated that CDKN2A was associated with the occurrence and development of tumors.CDKN2A in ACC was closely related to the sensitivity of various anti-tumor drugs and the immune checkpoint IDO1(cor=0.3,P<0.05),and it was positively correlated with the tumor mutation burden in ACC(R=0.49,P<0.01).Conclusion The cuprotosis-related gene CDKN2A is closely related to the prognosis,invasion,immune microenvironment,and drug sensitivity in ACC.

关 键 词：肾上腺皮质癌 生物信息学 铜死亡 CDKN2A 

分 类 号：Q811.4[生物学—生物工程] R736.6[医药卫生—肿瘤]