甲基转移酶样蛋白27是结肠癌预后的生物标志物并与免疫浸润相关

目的 探讨甲基转移酶样蛋白27（METTL27）在结肠癌中的表达、基因功能、免疫浸润和临床预后意义。方法 运用R语言，通过公共数据库TCGA、GEO、HPA数据库分析33种癌谱METTL27表达水平，并鉴定结肠癌中METTL27的差异基因，通过基因功能注释和富集分析鉴定相关信号通路；应用GSVA中的ssGSEA算法进行免疫浸润分析；Wilcoxon秩和检验(连续变量)、Logistic分析评价METTL27表达与临床病理特征的相关性；Kaplan-Meier分析、单因素和多因素Cox回归分析，构建列线图和校准图分析评价METTL27表达与临床预后的相关性。qPCR及Western blot实验验证METTL27在肠癌细胞株以及16例肠癌组织中的表达水平。结果 METTL27在21种肿瘤中显著高表达，结肠癌中METTL27的表达明显高于癌周组织（P<0.001）；METTL27进行差异分析，并鉴定了METTL27相关的差异基因，绘制了差异表达正负相关前10基因（P<0.001）；通过鉴定了METTL27的差异表达基因，初步对其进行了基因功能注释，发现METTL27在跨膜物质转运以及脂质代谢进程中显著富集，进一步GSEA识别了与之相关的5条信号通路；同时分析了METTL27表达与辅助T细胞、辅助T细胞2型、中央记忆型T细胞呈负相关关系（P<0.001）；在临床特征与预后分析中，METTL27 mRNA高表达的患者OS、DSS较差，Cox回归分析显示，METTL27表达是OS的独立预后因素；修改为：在不同肠癌细胞株以及16例肠癌组织样本中，METTL27的mRNA表达水平高于正常细胞及组织（P<0.05）；配对的4例肠癌组织蛋白检测也证实这一结果（P<0.001）。结论 METTL27在结肠癌中异常高表达，并代表了不良的临床预后；高表达的METTL27显示了更少的T细胞免疫浸润，提示METTL27可能为结肠癌的预后标记物。

METTL27 is a prognostic biomarker of colon cancer and associated with immune invasion

Objective To investigate the expression and gene function of methyltransferase-like protein 27 (METTL27) in colon cancer, its association with immune infiltration and its prognostic significance. Methods We analyzed the expression levels of METTL27 in 33 cancers using R language and identified METTL27 as a differential gene in colon cancer. The related signaling pathways of METTL27 were analyzed by gene functional annotation and enrichment. SsGSEA algorithm was used to analyze immune infiltration, and logistic analysis was used to evaluate the correlation between METTL27 expression and clinicopathological features of the patients. Kaplan-meier analysis, univariate and multivariate Cox regression analysis were performed to construct a nomogram for evaluating the correlation between METTL27 expression and clinical prognosis. The expression level of METTL27 was further verified in colorectal cancer cell lines and 16 clinical specimens of colorectal cancer tissues using qPCR and Western blotting. Results METTL27 was highly expressed in 21 cancers, and its expression was significantly higher in colon cancer than in adjacent tissues (P<0.001). METTL27-related genes were identified by differential analysis, and functional annotation revealed that METTL27 was significantly enriched in transmembrane transport and lipid metabolism, and 5 related signaling pathways were identified by GSEA. METTL27 expression was negatively correlated with different T helper cells and central memory T cells (P<0.001). The patients with a high METTL27 mRNA expression had a poor survival outcome. Cox regression analysis showed that METTL27 expression was an independent prognostic factor of the overall survival. The expression level of METTL27 was significantly higher in the colorectal cancer cell line than in normal cells (P<0.05). Conclusion METTL27 is overexpressed in colon cancer and is associated with a poor prognosis of the patients. A high expression of METTL27 showed is associated less T cell immune infiltration, suggesting the potential of METTL27 as a prognostic marker of colon cancer.