CDKN3在肿瘤中的表达及预后相关性分析  

Expression of CDKN3 in tumors and its correlation with prognosis

作　　者：陈邦捷 王欣仪 杨祎品 李海文 邵伟 顾康生[1] Chen Bangjie;Wang Xinyi;Yang Yipin;Li Haiwen;Shao Wei;Gu Kangsheng(Dept of Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei230022;Dept of Radiation Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei230022;Dept of Gastroenterology,The Third Affiliated Hospital of Anhui Medical University,Hefei230061;Dept of Pathogenic Biology,School of Basic Medical Sciences,Anhui Medical University,Hefei230032)

机构地区：[1]安徽医科大学第一附属医院肿瘤内科,合肥230022 [2]安徽医科大学第一附属医院肿瘤放疗科,合肥230022 [3]安徽医科大学第三附属医院消化内科,合肥230061 [4]安徽医科大学基础医学院病原生物学教研室,合肥230032

出　　处：《安徽医科大学学报》2024年第11期1944-1957,1966,共15页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金项目(编号:82071770);安徽省重点研究与开发计划项目(编号:202004j07020044);合肥市自然科学基金项目(编号:2022033)。

摘　　要：目的探讨细胞周期蛋白依赖性激酶抑制因子3(CDKN3)在不同肿瘤中的表达变化及其对肿瘤分期预后和免疫治疗的影响。方法使用TCGA、CCLE、ICGC和GTEx数据库评估CDKN3在不同肿瘤中的表达特征;采用GEPIA2平台和Kaplan-Meier法分别评估CDKN3对肿瘤病理分期和生存预后的影响;采用TIMER平台评估CDKN3对肿瘤免疫微环境和免疫治疗的影响,并利用生物信息学方法进一步探讨CDKN3对免疫检查点和免疫治疗关键预测指标的影响。GeneMANIA构建CDKN3的蛋白质-蛋白质相互作用(PPI)网络。京都基因和基因组百科全书(KEGG)以及基因本体(GO)数据库富集分析CDKN3相关的生物学过程和信号通路。通过转染CDKN3 siRNA验证CDKN3对HepG2细胞增殖、侵袭、迁移和凋亡的影响。结果CDKN3在肿瘤中普遍高表达。CDKN3的高表达通常与较晚的病理分期和不良的生存预后相关。CDKN3表达水平与绝大部分免疫检查点呈负相关,与肿瘤突变负荷(TMB)、微卫星不稳定(MSI)和碱基配对修复(MMR)基因呈正相关。CDKN3与细胞周期、细胞衰老和p53信号通路等相关。此外,EdU染色、JC-1染色、Transwell和Wound Healing实验证实CDKN3促进HCC细胞的增殖、侵袭和迁移,抑制其凋亡。结论CDKN3的异常表达与肿瘤的分期预后和免疫微环境特征密切相关,是一种潜在的肿瘤预后标志物和免疫治疗辅助靶点。Objective To investigate the expression changes of cyclin-dependent kinase inhibitor 3(CDKN3)in different tumors and its effect on tumor staging,prognosis and immunotherapy.Methods The expression characteristics of CDKN3 in different cancers using data from TCGA,CCLE,ICGC,and GTEx databases were evaluated.The GEPIA2 platform and Kaplan-Meier analysis were utilized to assess the effect of CDKN3 on tumor pathological staging and survival prognosis.The TIMER platform was employed to explore the influence of CDKN3 on the tumor immune microenvironment and immunotherapy.Its effect on immune checkpoint and key immunotherapeutic predictors using bioinformatics methods was explored.The GeneMANIA tool was used to construct the protein-protein interaction(PPI)network of CDKN3.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Onotology(GO)enrichment analyses were conducted to explore the biological processes and signaling pathways associated with CDKN3.The effect of CDKN3 on HepG2 cell proliferation,invasion,migration,and apoptosis was validated through transfection with CDKN3 siRNA.Results CDKN3 was found to be widely overexpressed in tumors.High expression of CDKN3 was often associated with advanced pathological staging and poor survival prognosis.CDKN3 expression was negatively correlated with most immune checkpoints and positively correlated with tumor mutation burden(TMB),microsatellite instability(MSI),and mismatch repair(MMR)genes.CDKN3 was associated with cell cycle,cellular senescence,and the p53 signaling pathway.Furthermore,EdU staining,JC-1 staining,Transwell,and Wound Healing assays confirmed that CDKN3 promoted HCC cell proliferation,invasion,and migration while inhibiting apoptosis.Conclusion Abnormal expression of CDKN3 is closely related to tumor staging,prognosis,and immune microenvironment characteristics,making it a potential prognostic marker and immunotherapy adjuvant target in cancer.

关 键 词：CDKN3 肿瘤 泛癌分析 预后评估 免疫治疗 生物标志物 肝细胞癌 

分 类 号：R730.49[医药卫生—肿瘤]