利用TCGA数据库分析COL11A1、MMP-11基因在膀胱癌中的表达及临床意义

Analysis of the clinical significance and expression of COL11A1 and MMP-11 genes in bladder cancer using TCGA database

目的探讨COL11A1、MMP-11基因与膀胱癌发展、预后的关系及意义。方法从TCGA数据库中下载膀胱癌中COL11A1、MMP-11基因表达谱及其临床信息并分析之间的关系。结果癌组织中COL11A1表达高于癌旁组织,但差异无统计学意义(P>0.05);癌组织中MMP-11表达高于癌旁组织,差异有统计学意义(P<0.05)。COL11A1、MMP-11表达均与年龄、T分期、N分期、病理分级、临床分期显著相关(P<0.05),均与M分期、性别无关(P>0.05)。COL11A1表达与总生存期、3年无瘤生存期、5年无瘤生存期无明显相关(P>0.05),但COL11A1低表达组的3、5年无瘤生存率(34.2%、33.4%)高于COL11A1高表达组(28.7%、28.0%),差异有统计学意义(P<0.05)。MMP-11表达与总生存期无明显相关(P>0.05),MMP-11表达与3、5年无瘤生存期均呈负相关(P<0.05);MMP-11低表达组的3、5年无瘤生存率(34.6%、33.9%)高于MMP-11高表达组(28.3%、27.5%),差异有统计学意义(P<0.05)。基因集富集分析结果显示,COL11A1高表达样本富集了细胞黏附因子、细胞外基质受体相互作用、黏着斑、白细胞跨上皮迁移、自然杀伤细胞介导的细胞毒性、细胞因子受体相互作用、趋化因子信号通路、T细胞受体信号通路等基因集。MMP-11高表达样本富集了细胞外基质受体相互作用、黏着斑、细胞黏附分子、白细胞跨上皮迁移、细胞因子受体相互作用、癌症通路、趋化因子信号通路、溶酶体等基因集。结论COL11A1、MMP-11可能作为膀胱癌进展的标志物,其高表达是膀胱癌进展及不良预后的危险因素。

Objective To explore the relationship and significance of COL11A1 and MMP-11 genes with the progression and prognosis of bladder cancer.Methods The expressions profile and clinical information of COL11A1,MMP-11 genes in bladder cancer were downloaded from TCGA database,and the relationship between them was analyzed.Results The expression of COL11A1 in cancer tissue was higher than that in adjacent tissue,but the difference was not statistically significant(P>0.05);the expression of MMP-11 in cancer tissue was higher than that in adjacent tissue,the difference was statistically significant(P<0.05).The expressions of COL11A1 and MMP-11 were significantly correlated with age,T stage,N stage,pathological grade and clinical stage(P<0.05),and were not related to M stage and gender(P>0.05).The expressions of COL11A1 were not significantly associated with overall survival,3-year tumor-free survival,and 5-year tumor-free survival(P>0.05),but 3-year tumor-free survival rate,5-year tumor-free survival rate in the COL11A1 low expression group(34.2%,33.4%)were higher than those of the COL11A1 high expression group(28.7%,28.0%),the differences were statistically significant(P<0.05).The expression of MMP-11 was not significantly correlated with overall survival(P>0.05),but that were negatively correlated with 3-year tumor-free survival and 5-year tumor-free survival(P<0.05);the 3-year tumor-free survival rate and 5-year tumor-free survival rate in the MMP-11 low expression group(34.6%,33.9%)were higher than those of the MMP-11 high expression group(28.3%,27.5%),the differences were statistically significant(P<0.05).The results of gene set enrichment analysis(GSEA)showed those COL11A1 high expression samples were enriched in cell adhesion molecules cams,ecm receptor interaction,focal adhesion,leukocyte transendothelial migration,natural killer cell mediated cytotoxicity,cytokine cytokine receptor interaction,chemokine signaling pathway and T cell receptor signaling pathway.The MMP-11 high expression samples were enriched gene sets such as ecm receptor interaction,focal adhesion,cell adhesion molecules cams,leukocyte transendothelial migration,cytokine cytokine receptor interaction,pathways in cance,chemokine signaling pathway,and lysosome.Conclusion COL11A1 and MMP-11 may be used as markers of bladder cancer progression,and their high expressions are a risk factor for bladder cancer progression and poor prognosis.