首页|锌指蛋白488在结肠癌中的临床意义及其对免疫浸润的影响

锌指蛋白488在结肠癌中的临床意义及其对免疫浸润的影响

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目的 探讨锌指蛋白488(ZNF488)在结肠癌中的表达对临床意义及其对结肠癌免疫微环境的影响.方法 利用癌症基因组图谱数据库分析ZNF488在结肠癌中的表达模式.采用人正常结肠上皮细胞系和结肠癌细胞系和实时荧光定量聚合酶链反应(RT-qPCR)检测结肠癌中ZNF488的表达水平.通过Kaplan-Meier和Cox回归分析探讨ZNF488表达对结肠癌患者预后的影响.采用单样本GSEA(ssGSEA)免疫浸润算法分析结肠癌微环境中的免疫细胞浸润网络.小干扰RN A(siRNA)转染下调SW620结肠癌细胞株中ZNF488表达,通过细胞计数试剂盒(CCK-8)和克隆形成实验检测ZNF488对结肠癌细胞增殖的影响;通过划痕实验和Transwell实验验证ZNF488对结肠癌细胞迁移的影响.组间比较采用Wilcoxon秩和检验、Student'st检验或方差分析.结果 结肠癌组织中ZNF488表达水平高于癌旁组织(非配对样本:1.282±0.816比1.668±1.058,t=2.28,P<0.05;配对样本:0.645±0.600 比 0.864±0.626,U=273,P<0.05),RT-qPCR 结果显示,与NCM460 比较,SW260 的 ZNF488 显著性高表达(1.051±0.097 比 4.733±0.088,t=48.76,P<0.01).高ZNF488表达与结肠癌患者预后不良相关,总体生存期[风险比(hazard rate,HR)=1.68,P<0.05]显著缩短,同时,ZNF488是影响结肠癌患者预后的独立危险因素(总生存期,HR=2.079,P<0.01).高ZNF488表达与结肠癌患者CD56bright自然杀伤细胞(R=0.343,P<0.01)程度呈正相关.干扰 ZNF488 后(1.000±0.042 比 0.322±0.026,t=23.70,P<0.01),差异有统计学意义;CCK-8(24 h:0.279±0.015 比 0.213±0.007,t=7.01,P<0.01;48 h:0.876±0.022 比 0.383±0.006,t=37.96,P<0.01);克隆形成实验(420.000±15.875 比 287.000±15.716,t=10.31,P<0.01);Transwell(239.667±3.786 比 129.667±25.716,t=7.33,P<0.01);划痕实验(24 h:0.012±0.003 比 0.002±0.001,t=4.475,P<0.05;48 h:0.052±0.013 比 0.026±0.004,t=3.22,P<0.05).结论 ZNF488高表达与结肠癌预后不良相关,并可能参与肿瘤免疫调控及促进结肠癌细胞的增殖和迁移.
Clinical significance of Zinc finger protein 488 expression in colon adenocarcinoma and its impact on the immune microenvironment
Objective This study aims to investigate the clinical significance of Zinc finger protein 488(ZNF488)expression in colorectal cancer and its impact on the immune microenvironment of colon cancer.Methods The Cancer Genome Atlas database was utilized explore the expression pattern of ZNF488 in colon cancer.The expression of ZNF488 in colon cancer was detected using normal colon epi-thelial cell line and various colon cancer cell lines by real-time quantitative polymerase chain reaction(RT-qPCR).The impact of ZNF488 expression on the prognosis of colon cancer patients was analyzed u-sing Kaplan-Meier and Cox regression analysis.Single-sample Gene Set Enrichment Analysis(ssGSEA)immune infiltration algorithm was employed to analyze the immune cell infiltration network in colorectal cancer microenvironment.The expression of ZNF488 in SW620 colon cancer cell line was interfered by small interfering RNA(siRNA),then cell counting kit-8(CCK-8)and Clone formation assays were per-formed to explore the effect of ZNF488 on cell proliferation,and Transwell and wound-healing assays were employed to verify the impact of ZNF488 on colon cancer cell migration.Intergroup comparisons were con-ducted using the Wilcoxon rank-sum test,Student's t-test or analysis of variance.Results The expression level of ZNF488 in colon cancer tissues was higher than that in adjacent non-cancerous tissues(non-paired samples:1.282±0.816 vs.1.668±1.058,t=2.28,P<0.05;paired samples:0.645±0.600 vs.0.864±0.626,U=273,P<0.05).compared to NCM460,the RT-qPCR results indicated higher expres-sion of ZNF488 in SW260(1.051±0.097 vs.4.733±0.088,t=48.76,P<0.01).Colon cancer pa-tients with high ZNF488 expression had worse prognosis,with significantly shortened overall survival[haz-ard ratio(HR)=1.68,P<0.05].Moreover,ZNF488 was identified as an independent risk factor affect-ing the prognosis of colon cancer patients(overall survival,HR=2.079,P<0.01).Colon cancer patients with high ZNF488 expression showed a positive correlation with the degree of infiltration of CD56bright nat-ural killer cells(R=0.343,P<0.01).After interfering with ZNF488(1.000±0.042 vs.0.322±0.026,t=23.70,P<0.01),significant differences were observed;the CCK-8 assay(24 h:0.279±0.015 vs.0.213±0.007,t=7.01,P<0.01;48 h:0.876±0.022 vs.0.383±0.006,t=37.96,P<0.01);colony formation assay(420.000±15.875 vs.287.000±15.716,t=10.31,P<0.01);Tran-swell(239.667±3.786 vs.129.667±25.716,t=7.33,P<0.01);scratch assays(24 h:0.012±0.003 vs.0.002±0.001,t=4.48,P<0.05;48 h:0.052±0.013 vs.0.026±0.004,t=3.22,P<0.05).Conclusion High expression of ZNF488 is associated with poor prognosis in colon cancer and may be involved in tumor immune regulation and promotion of colon cancer cell proliferation and migration.

Zinc finger protein 488Colon cancerPrognosisImmune microenvironment

龚成林、温玉刚

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上海交通大学医学院附属第一人民医院普外科,上海 200080

锌指蛋白488 结肠癌 预后 免疫微环境

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(12)