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胶原十二型α1链在结肠癌中的表达及意义

Expression and significance of collagen type Ⅻ α1 chain in colon cancer

    摘要
  • 摘要:
    目的 探讨胶原十二型α1链(COL12A1)在结肠癌组织中的表达及其与结肠癌患者临床病理学特征、预后的关系。
    方法 采用癌症基因组图谱(TCGA)数据库分析结肠癌组织与癌旁组织的COL12A1表达水平差异，采用TIMER数据库分析COL12A1与肿瘤微环境、免疫浸润的关系。利用基因集富集分析(GSEA)探讨COL12A1在结肠癌中发挥其生物学功能所依赖的相关信号通路。采用免疫组织化学(IHC)评估47例结肠癌及癌旁正常结肠黏膜组织中COL12A1的表达水平，并分析其与结肠癌患者临床病理学特征的关系; 采用蛋白印迹法(WB)检测结肠癌细胞系和正常结肠黏膜细胞系中COL12A1表达水平。利用GEPIA和PrognoScan在线分析网站分析COL12A1表达与结肠癌患者预后的关系。
    结果 TCGA数据库结肠癌数据集分析显示, COL12A1在结肠癌组织中的表达高于正常组织，差异有统计学意义(P < 0.001); IHC结果显示, COL12A1在结肠癌组织中的表达高于癌旁正常组织，差异有统计学意义(P < 0.000 1)。在结肠癌组织中, COL12A1表达水平与神经/血管浸润(P=0.029)、淋巴结转移(P=0.003)、TNM分期(P=0.001)有关。在线数据库分析显示, COL12A1高表达患者的无病生存期较短。COL12A1表达与结肠癌微环境中CD8+T细胞、B细胞、CD4+T细胞、巨噬细胞、嗜酸性粒细胞、中性粒细胞及树突状细胞呈正相关(P < 0.001)。基因本体论(GO)及京都基因和基因组百科全书(KEGG)通路分析表明, COL12A1表达涉及细胞黏附、化学突触传递、细胞因子受体相互作用、细胞基质受体相互作用、自噬调节等信号通路。
    结论 COL12A1在结肠癌细胞系及组织中呈高表达，并且与患者不良预后呈正相关。COL12A1的表达与结肠癌微环境的免疫细胞浸润呈正相关, COL12A1或可作为结肠癌预后的一种新的标志物，并可能成为免疫治疗的潜在靶点。

     

    Abstract:
    Objective To investigate the expression of collagen type Ⅻ α1 chain (COL12A1) in tissues of colon cancer and its relationships with clinicopathological characteristics and prognosis of patients with colon cancer.
    Methods The difference of COL12A1 expression level between colon cancer tissues and adjacent tissues was analyzed by The Cancer Genome Atlas (TCGA) database, and the relationships of COL12A1 with tumor microenvironment and immune invasion were analyzed by the TIMER database. Gene Set Enrichment Analysis (GSEA) was used to explore the related signal pathways of COL12A1 playing its biological functions in colon cancer. Immunohistochemistry (IHC) was used to evaluate the expression of COL12A1 in 47 cases of colon cancer and normal colon mucosa adjacent to the cancer, and its relationship with the clinicopathological characteristics of colon cancer patients was analyzed as well; the Western blot (WB) was used to detect the expression level of COL12A1 in colon cancer cell lines and normal colon mucosa cell lines. GEPIA and PrognoScan online analysis websites were used to analyze the relationship between the expression of COL12A1 and the prognosis in patients with colon cancer.
    Results The analysis of colon cancer dataset of TCGA database showed that the expression of COL12A1 in colon cancer tissues was significantly higher than that in normal tissues (P < 0.001); the IHC result showed that the expression of COL12A1 in colon cancer tissues was significantly higher than that in normal adjacent tissues (P < 0.000 1). In colon cancer tissues, the expression level of COL12A1 was related to nerve or vascular invasion (P=0.029), lymph node metastasis (P=0.003), and TNM staging (P=0.001). Online database analysis showed that patients with high expression of COL12A1 had a shorter disease-free survival. The expression of COL12A1 was positively correlated with CD8+ T cells, B cells, CD4+ T cells, macrophages, eosinophils, neutrophils and dendritic cells in colon cancer microenvironment (P < 0.001). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that COL12A1 expression involved in signal pathways such as cell adhesion, chemical synaptic transmission, cytokine receptor interaction, cell matrix receptor interaction and autophagy regulation.
    Conclusion COL12A1 is highly expressed in colon cancer cell lines and tissues, and is positively related to the poor prognosis of patients. The expression of COL12A1 is positively correlated with the immune cell infiltration of colon cancer microenvironment, and COL12A1 may be a new prognostic marker for colon cancer and a potential target for immunotherapy.

     

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