Wang K, Zhang J, Deng M, Ju Y, Ouyang M
Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University, Foshan 528308, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Apr 20;42(4):486-497. doi: 10.12122/j.issn.1673-4254.2022.04.04.
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.
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.
METTL27 was highly expressed in 21 cancers, and its expression was significantly higher in colon cancer than in adjacent tissues ( < 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 ( < 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 ( < 0.05).
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.
探讨甲基转移酶样蛋白27(METTL27)在结肠癌中的表达及基因功能、其与免疫浸润的关系及其预后意义。
我们使用R语言分析了33种癌症中METTL27的表达水平,并将METTL27鉴定为结肠癌中的差异基因。通过基因功能注释和富集分析METTL27的相关信号通路。采用单样本基因集富集分析(SsGSEA)算法分析免疫浸润情况,并采用逻辑分析评估METTL27表达与患者临床病理特征之间的相关性。进行Kaplan-Meier分析、单因素和多因素Cox回归分析,构建用于评估METTL27表达与临床预后相关性的列线图。使用实时定量聚合酶链反应(qPCR)和蛋白质免疫印迹法(Western blotting)在结肠癌细胞系和16例结直肠癌组织临床标本中进一步验证METTL27的表达水平。
METTL27在21种癌症中高表达,其在结肠癌中的表达明显高于癌旁组织(<0.001)。通过差异分析鉴定出METTL27相关基因,功能注释显示METTL27在跨膜转运和脂质代谢中显著富集,基因集富集分析(GSEA)鉴定出5条相关信号通路。METTL27表达与不同的辅助性T细胞和中枢记忆T细胞呈负相关(<0.001)。METTL27 mRNA高表达的患者生存结局较差。Cox回归分析表明,METTL27表达是总生存的独立预后因素。结肠癌细胞系中METTL27的表达水平明显高于正常细胞(<0.05)。
METTL27在结肠癌中过表达,与患者预后不良相关。METTL27高表达显示T细胞免疫浸润较少,提示METTL27作为结肠癌预后标志物的潜力。