Runt相关转录因子2在人肾透明细胞癌组织的表达及其临床意义

Expression and clinical significance of runt-related transcription factor 2 in human renal clear cell carcinoma

目的探讨Runt相关转录因子2(RUNX2)在肾透明细胞癌(ccRCC)中的表达及其与患者预后和临床病理特征之间的关系。方法基于肾癌肿瘤基因组图谱(TCGA)数据, 分析RUNX2在癌和癌旁组织中的表达及其预后价值。采用多色免疫荧光标记(mIHC)技术分析RUNX2在癌和癌旁组织中的分布特征, 并结合临床资料进行χ2检验。单因素和拟合多因素Cox模型分析RUNX2及其他指标的预后价值。基于TCGA数据库, 探讨RUNX2与免疫细胞浸润的相关性。结果 TCGA数据分析结果显示, RUNX2在癌组织中的表达显著高于正常组织(P<0.001)。mIHC结果表明RUNX2在癌组织表达水平高于癌旁组织(Z=-2.123, P<0.05), 且其表达水平与患者总生存期呈负相关[P<0.01, 风险比(HR)=2.768, 95%可信区间(CI):1.120~6.838]。RUNX2表达水平与患者美国癌症联合委员会(AJCC)临床分期明显相关(χ2=4.505, P<0.05)。多因素Cox回归模型显示年龄(P<0.01, HR=1.068, 95%CI:1.024~1.113)、病理分级(P<0.05, HR=2.171, 95%CI:1.179~3.997)和AJCC分期(P<0.05, HR=4.638, 95%CI:1.086~19.793)均可以作为肾癌患者的独立预后因素。基于TCGA数据库分析, 证实肾癌组织中RUNX2与多种免疫细胞的浸润程度相关。结论 RUNX2高表达与肾癌患者不良预后明显相关。

Objective To study the expression of runt-related transcription factor 2(RUNX2)in clear cell renal cell carcinoma(ccRCC)and evaluate the relationship between RUNX2 and the prognosis and clinical parameters of patients.Methods Based on the cancer genome atlas(TCGA)data of ccRCC,the expression level and prognostic value of RUNX2 in tumor tissues and adjacent normal tissues were analyzed.Multiplex Immunohistochemistry(mIHC)technique was used to analyze the expression features of RUNX2 in tumor tissues and adjacent normal tissues.The chi-square test was performed in combination with clinical data.Univariate and multivariate Cox models were used to analyze the prognostic value of RUNX2 and other indicators.The TCGA database was used to analyze the correlation between RUNX2 and immune cells infiltration.Results The TCGA data showed that the expression of RUNX2 in tumor tissues was higher than in adjacent normal tissues(P<0.001).The results of mIHC staining showed that the expression level of RUNX2 in cancer tissues was higher than that in adjacent tissues(Z=-2.123,P<0.05),and its expression level was negatively correlated with the overall survival of patients[P<0.01,hazard ratio(HR)=2.768,95%confidence interval(CI):1.120-6.838].The expression level of RUNX2 was obviously correlated with American Joint Committee on Cancer(AJCC)stage(χ2=4.505,P<0.05).Cox model demonstrated that age(P<0.01,HR=1.068,95%CI:1.024-1.113),pathological grade(P<0.05,HR=2.171,95%CI:1.178-3.997)and AJCC grade(P<0.05,HR=4.638,95%CI:1.086-19.793)could serve as independent prognostic factors for ccRCC patients.In addition,the expression of RUNX2 was proved to be associated with multiple immune cells infiltration based on TCGA database analysis.Conclusion The high expression of RUNX2 is significantly related to the poorer prognosis of ccRCC patients.