结肠癌中SERPINE1的表达、预后及作用机制

SERPINE1's expression and prognosis in Colon Cancer and its mechanism of action

目的:探究丝氨酸蛋白酶抑制剂1(SERPINE1)在结肠癌中的表达差异与预后关系及分子生物学机制。方法:从TCGA和GTEx数据库获得样本RNAseq数据和临床信息后,根据不同分组进行SERPINE1表达与预后生存分析、预后模型单因素和多因素Cox回归分析及与通路基因相关性分析。结果:(1)SERPINE1在结肠癌中高表达(P<0.01);(2)在年龄、性别、种族及复发类型分组中表达无统计学差异(P>0.05),而在有无淋巴结转移、远处转移及pTNM分期中其表达有明显统计学差异(P<0.01),且对预后生存有显著影响(P<0.01);(3)在高、低表达组预后分析中表明高表达组PFS时间短,风险系数高(P<0.01);(4)在预后模型单因素和多因素Cox回归分析表明SERPINE1是预后生存的独立危险因素(P<0.05);(5)通过SERPINE1基因与通路评分间的Spearman相关性分析表明与EMT、血管生成、ECM的降解分子机制相关性较强(P<0.01,r>0.6)。结论:SERPINE1在结肠癌中高表达,在伴有淋巴转移,远处转移及晚期患者中表达更高,且提示患者预后生存不良,是判断预后的独立危险因素。此外,SERPINE1可能通过参与EMT、肿瘤血管生成及ECM降解的信号通路介导结肠癌的发生与进展。SERPINE1可能是结肠癌诊断、治疗和预后判断的潜在新分子。

Objective:To explore the relationship between the differential expression of serine protease inhibitor 1(SERPINE1)and prognosis in colon cancer and its molecular biological mechanism.Methods:After obtaining sample RNAseq data and clinical information from TCGA and GTEx databases,SERPINE1 expression and prognostic survival analysis,univariate and multivariate Cox regression analysis and its correlation with pathway genes were performed according to the grouping.Results:(1)SERPINE1 was highly expressed in patients with colon cancer.(2)There was no significant difference in age,sex,race and recurrence type,but there was significant difference in lymph node metastasis,distant metastasis and pTNM stage(P<0.01),and had significant effect on prognosis and survival(P<0.01).(3)The prognostic analysis of high and low expression groups showed that the non-progressive survival time was short and the risk coefficient was high in the high expression group,and vice versa.(4)Univariate and multivariate Cox regression analysis showed that SERPINE1 was an independent risk factor for prognostic survival.(5)The Spearman correlation analysis between SERPINE1 gene and pathway score showed that it was strongly correlated with the molecular mechanism of epithelial mesenchymal cell transformation(EMT),angiogenesis and extracellular matrix(ECM)degradation(P<0.01,r>0.6).Conclusion:The expression of SERPINE1 is increased in colon cancer,especially in patients with lymphatic metastasis,distant metastasis and advanced stage,which suggests that the prognosis of patients is poor,which is an independent risk factor for prognosis.In addition,SERPINE1 may be involved in EMT,tumor angiogenesis and ECM degradation in the occurrence and development of colon cancer.SERPINE1 may be a potential new molecule in the diagnosis,treatment and prognosis of colon cancer.