基于TCGA数据库探讨NKAIN1表达增高与子宫内膜癌预后的关系

Increased Expression of NKAIN1 in Endometrial Carcinoma Predicts Poor Prognosis:An Analysis Based on Studies from TCGA Datasets

目的:探讨NKAIN1基因在子宫内膜癌患者组织中的表达与临床病理参数及预后的相关性。方法:利用TCGA数据库评价NKAIN1在子宫内膜癌发生发展中的作用。通过Wilcox(或Krustal)检验和逻辑回归的方法分析NKAIN1表达与临床病理参数之间的关系。采用Cox回归和Kaplan-Meier法评估各个临床病理特征包括NKAIN1的表达与总体生存率之间的关系。最后再利用TCGA进行基因集富集分析(gene set enrichment analysis,GSEA)。结果:TCGA数据库证实子宫内膜癌组织中NKAIN1表达水平明显高于正常内膜组织(P<0.001)。NKAIN1高表达与肿瘤分期(OR=2.04,III期/IV期vs I期/II期),分级(OR=2.41,中分化/低分化vs高分化),携瘤状态(OR=2.11,带瘤vs无瘤),腹水细胞学(OR=3.29,阳性vs阴性)及组织学类型(OR=3.49,浆液性腺癌/浆液性与子宫内膜样混合型腺癌vs子宫内膜样腺癌)等明显相关(P均<0.05)。Kaplan-Meier生存分析表明NKAIN1高表达组较低表达组总生存期偏短(P<0.001)。单因素分析表明NKAIN1高表达与子宫内膜癌的不良生存预后相关(HR:1.04;CI:1~1.08,P=0.016);多因素分析进一步证明NKAIN1高表达可作为独立的预后因子预测子宫内膜癌的不良结局(HR=1.05;CI:1.01~1.1;P=0.013)。GSEA分析提示NKAIN1基因高表达主要富集了细胞周期及剪接体通路。结论:NKAIN1基因高表达可能与进展期的子宫内膜癌相关,并有望成为子宫内膜癌不良预后结局的潜在的分子标志物。

Objective:To identify the association of NKAIN1 expression with clinicopathological parameters and prognosis in endometrial carcinoma(EC)patients.Methods:We evaluated the role of NKAIN1 in EC using data publicly available from The Cancer Genome Atlas(TCGA).The relationships between clinicopathologic characteristics and NKAIN1 were analyzed by the Wilcoxon test(or Kruskal-Wallis rank sum test)and logistic regression.Cox regression and Kaplan-Meier method were used to analyze the relationship between clinico-pathologic features and overall survival(OS)of TCGA pa-tients.Gene Set Enrichment Analysis(GSEA)was also conducted by using data from TCGA.Results:Increased NKAIN1 expression in EC was significantly correlated with stage(OR=2.04;III/IV vs I/II),grade(OR=2.41;moderate/poor vs well),status(OR=2.11;with tumor vs tumor free),peri-toneal cytology(OR=3.29;positive vs negative)and histology(OR=3.49;serous/mixed vs endometrioid)(all P<0.05).Kaplan-Meier survival analysis revealed that EC with high NKAIN1 expression had a worse prognosis than that with low NKAIN1 expression(P<0.001).Univariate analyses showed that high NKAIN1 expression was significantly associated with a poor OS(HR:1.04;95%CI:1-1.08;P=0.016).Multivariate analysis showed that NKAIN1 remained independently associated with OS(HR:1.05;CI:1.01-1.1;P=0.013).GSEA revealed that cell cycle and spliceosome were differen-tially enriched in the NKAIN1 high expression group.Conclusion:NKAIN1 expression may correlate with the development of EC,and its high expression might be used as a potential prognostic molecular marker of poor survival in EC.