TPX2的表达对胰腺癌预后的影响

Effect of TPX2 expression on prognosis of pancreatic carcinoma

目的研究Xklp2靶蛋白(TPX2)在胰腺癌中的表达情况及其预测预后的潜在价值。方法基于200个糖酵解代谢相关基因,从TCGA和GEO数据库获取胰腺患者的信息,对后者的糖酵解代谢特征进行评价,同时综合患者代谢特征及差异基因,采用Cox回归和Lasso回归分析建立风险模型,获得关键糖酵解相关基因TPX2,并用GEO数据库验证该模型的预后有效性。基于预后基因的表达分析胰腺癌患者的生存期,并分析正常胰腺组织和胰腺癌中预后基因的表达差异,最后在细胞水平验证预后基因的功能。结果病例队列被分为高、中、低3个糖酵解代谢特征组,低速率糖酵解代谢患者存在一定生存优势,TPX2是该模型的关键基因,胰腺癌患者显示高表达TPX2,具有较差的预后。细胞水平上敲降TPX2可抑制胰腺癌细胞增殖和集落形成。结论本研究基于糖酵解代谢模型有效地预测了胰腺癌患者的预后,TPX2有望成为胰腺癌预后预测的潜在标志性基因。

Objective To study the expression of Xklp2 target protein(targeting protein for Xenopus kinesin-like protein2,TPX2)in pancreatic carcinoma and its potential value in predicting prognosis.Methods Based on 200 genes related to glycolysis,the information of pancreatic patients was obtained from TCGA and GEO databases,and the characteristics of glycolysis metabolism of the latter were evaluated.At the same time,the metabolic characteristics and differential genes of the patients were evaluated,the risk model was established by Cox regression and Lasso regression analysis,and the key glycolysis related gene TPX2 was obtained.The prognostic validity of the model was verified by GEO database based on the expression of prognostic genes,the overall survival(OS)of patients with pancreatic cancer,the difference in the expression of prognostic genes between normal pancreatic tissue and pancreatic cancer was analyzed and finally the function of prognostic genes was verified at the cellular level.Results The case cohort was divided into three characteristic groups:high,medium and low glycolysis metabolism.Patients with low-rate glycolysis metabolism had certain survival advantages.TPX2 was the key gene of this model.Pancreatic cancer patients showed high expression of TPX2 and had poor prognosis.Knocking down TPX2 at cellular level can inhibit the proliferation and colony formation of pancreatic cancer cells.Conclusions The model based on glycolysis metabolism can effectively predict the prognosis of patients with pancreatic cancer.TPX2 is expected to become a potential marker gene for predicting the prognosis of pancreatic cancer.