KDM4C在结肠癌中的表达及临床意义  

Expression and clinical significance of KDM4C in colorectal cancer

作　　者：曾兵 李锦宏 辛海洋[4] 刘付恒 元志龙 甘文昌[1,2,3] 蔡灿锋 李英儒 Bing Zeng;Jinhong Li;Haiyang Xin;Fuheng Liu;Zhilong Yuan;Wenchang Gan;Canfeng Cai;Yingru Li(Department of General Surgery,Hernia and Abdominal Wall Surgery,Sun Yatsen University,Guangzhou 510655,China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,Sun Yatsen University,Guangzhou 510655,China;Biomedical Innovation Center,the Sixth Affiliated Hospital,Sun Yatsen University,Guangzhou 510655,China;Department of General Surgery,Department of Gastrointestinal Surgery,Affiliated Qingyuan Hospital,the Sixth Clinical Medical School,Guangzhou Medical University,Qingyuan People's Hospital,Qingyuan 511518,China)

机构地区：[1]中山大学附属第六医院普通外科疝和腹壁外科,广州510655 [2]广东省结直肠盆底疾病研究重点实验室,广州510655 [3]广州市黄埔区中六生物医学创新研究院,广州510655 [4]广州医科大学附属清远医院(清远市人民医院)普通外科胃肠外科,511518

出　　处：《中华结直肠疾病电子杂志》2025年第1期53-61,共9页Chinese Journal of Colorectal Diseases(Electronic Edition)

基　　金：国家临床重点专科项目;国家自然科学基金项目(No.81973858,No.82172790);广东省自然科学基金项目(No.2019A1515011200);广东省消化系统疾病临床医学研究中心项目(No.2020B1111170004);广东省中医药局科研课题(No.20211086,No.20221094);广东省医学科学技术研究基金项目(No.A2021061);广州市科技计划项目(No.2023A04J1816)。

摘　　要：目的探讨赖氨酸特异性组蛋白去甲基化酶4C(KDM4C)在结肠癌组织中的表达及临床意义。方法采用免疫组化染色法检测KDM4C在结肠癌组织及癌旁组织中的表达,分析KDM4C表达与临床病理因素以及预后的关系。利用TCGA数据库分析KDM4C在结肠癌组织与正常组织中的差异表达,Kaplan-Meier法分析其与结肠癌生存预后的关系。GSE108989单细胞数据分析KDM4C在各细胞群中的分布。采用quanTIseq法分析KDM4C与结肠癌组织中免疫细胞浸润之间的关系。CCK-8实验检测KDM4C对结肠癌细胞增殖和药物敏感性的影响。结果免疫组化结果显示KDM4C在结肠癌组织中的表达高于癌旁组织(Z=-5.722,P<0.001)。KDM4C表达与肿瘤大小(χ2=6.473,P=0.011)、浸润深度(χ2=4.146,P=0.020)、淋巴结转移(χ2=6.473,P=0.011)、TMN分期(χ2=5.840,P=0.016)以及化疗耐药(χ2=5.38,P=0.032)相关。TCGA数据库分析显示KDM4C mRNA在结肠癌组织中的表达显著高于正常结肠黏膜组织(Z=-2.297,P=0.021)。生存分析显示KDM4C高表达患者的总生存率显著低于低表达组,差异有统计学意义(χ2=6.772,P=0.0093)。亚组分析显示,在右半结肠癌中KDM4C高表达组患者总生存率显著低于低表达组(χ2=4.691,P=0.0303)。GSE108989单细胞测序分析显示KDM4C在CD4Tconv、CD8T、CD8Tex、Tprolif以及Treg细胞中均有表达。免疫浸润分析显示KDM4C的表达与B细胞、M2型巨噬细胞、中性粒细胞、Treg细胞等浸润相关。下调KDM4C的表达可抑制结肠癌细胞HCT116和SW480的增殖活力,以及增强结肠癌细胞对奥沙利铂的敏感性。结论KDM4C在结肠癌组织中高表达,与不良生存预后相关。下调KDM4C可抑制肠癌细胞的增殖活力,以及增强肠癌细胞的化疗敏感性。Objective To investigate the expression of KDM4C in colon cancer tissue and its clinical implications.Methods The expression of KDM4C in colon cancer was detected using immunohistochemistry.The relationship between KDM4C and clinical pathological factors as well as prognosis was analyzed.The expression status of KDM4C was also analyzed using TCGA database,and its relationship with survival prognosis was further investigated using the Kaplan-Meier method.Single-cell analysis from GSE108989 was performed to examine the distribution of KDM4C across various cell types.A quanTIseq approach was utilized to explore the correlation between KDM4C and immune cell infiltration in colon cancer.The effect of KDM4C on the proliferation and drug sensitivity of cancer cells was assessed using CCK-8 experiment.Results KDM4C expression in colon cancer tissues was higher than that in adjacent non-cancerous tissues(Z=-5.722,P<0.001).The expression of KDM4C was correlated with tumor size(χ2=6.473,P=0.011),invasion depth(χ2=4.146,P=0.020),lymph node metastasis(χ2=6.473,P=0.011),TNM staging(χ2=5.840,P=0.016),and chemotherapy resistance(χ2=5.38,P=0.032).TCGA database revealed significantly higher expression of KDM4C mRNA in colon cancer compared to normal colon mucosal tissue(Z=-2.297,P<0.001).Survival analysis indicated that patients with high KDM4C expression had a significantly lower overall survival rate compared to those with low expression,the difference being statistically significant.Subgroup analysis revealed that patients with high KDM4C expression in right-sided colon cancer had significantly lower overall survival compared to those with low expression,(χ2=4.691,P=0.0303).Single-cell sequencing analysis of GSE108989 showed that KDM4C was expressed in CD4Tconv,CD8T,CD8Tex,Tprolif,and Treg cells.Immunoinfiltration analysis revealed that KDM4C expression was associated with infiltration by B cells,M2 macrophages,neutrophils,and Tregs.Downregulation of KDM4C expression inhibited the proliferation activity of colorectal canc

关 键 词：结肠肿瘤 赖氨酸特异性组蛋白去甲基化酶4C 预后 

分 类 号：R735.3[医药卫生—肿瘤]