PBK基因在膀胱癌中的表达及临床意义

Expression of PBK gene in bladder cancer and its clinicopathological characteristics

目的探讨PBK基因表达对膀胱癌患者临床病理特征及预后的影响,并寻找膀胱癌诊治的新靶点。方法在GEO数据库中下载膀胱癌样本资料GSE13507及相关临床信息。通过两独立样本t检验分析PBK在膀胱癌组织和正常膀胱组织中的表达差异,运用2检验研究PBK的表达与膀胱癌临床病理特征的相关性;并应用Kaplan-Meier法和对数秩检验进行生存分析,最后运用基因集富集分析(GSEA)寻找PBK调控膀胱癌细胞的相关通路。结果与正常膀胱组织比较,PBK在膀胱癌细胞中高表达(P<0.001);PBK的高表达与膀胱癌患者性别(P<0.001),年龄(P=0.027),侵袭性(P<0.001),高分级(P<0.001),T分期(P=0.001),N分期(P=0.015),M分期(P<0.001),疾病进展(P<0.001)和疾病复发(P<0.001)显著相关。PBK高表达患者的总生存期(P=0.0023)和肿瘤特异性生存期(P=0.0003)显著低于低表达患者。GSEA的结果显示PBK可能通过调节MYC信号通路、G2M检查点、精子发生、E2F转录因子、未折叠蛋白反应等影响膀胱癌的发生发展。结论PBK在膀胱癌中高表达,与膀胱癌的多个临床病理特征相关,可能成为膀胱癌新型肿瘤标志物或者治疗靶点。

Objective To investigate the relationship of expression of PDZ-binding kinase(PBK)gene and the clinical outcomes of bladder cancer(BC)patients and to provide new markers for diagnosis and treatment.Methods Two independent samples t test,Chi-square test and log-rank-based survival analysis were performed using public BC data GSE13507.Moreover,gene set enrichment analysis(GSEA)was applied to study relevant mechanisms.Results Two independent samples t test results suggested that PBK was upregulated in BC cells when compared with normal bladder tissues(P<0.001).Chi-square test indicated that higher expression of PBK was associated with the gender,age,invasiveness,higher grade,T staging,N staging,M staging,disease progression and relapse.BC patients with higher PBK expression had significantly worse overall survival(P=0.0023)and cancer specific survival(P=0.0003).GSEA results indicated that PBK may affect the prognosis of BC patients through“MYC targets”,“G2M checkpoint”,“spermatogenesis”,“E2F targets”,“unfolded protein response”.Conclusion PBK expression is correlated with many poor clinicopathological characteristics and prognosis,and it may be a new biomarkers of diagnosis and treatment for BC.