Cui Kun, Yao Xi, Wei Zhengbo, Yang Yujia, Liu Xinli, Huang Zhongheng, Huo Huimin, Tang Jinping, Xie Ying
Guangxi Key Laboratory of High-Incidence Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, China.
Life Sciences Institute of Guangxi Medical University, Nanning, Guangxi, China.
Front Genet. 2022 Sep 15;13:917344. doi: 10.3389/fgene.2022.917344. eCollection 2022.
Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time. Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB. In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels. HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.
吲哚乙胺 - N - 甲基转移酶（INMT）是一种甲基转移酶，负责将甲基从甲基供体S - 腺苷甲硫氨酸（SAM）转移至其底物。SAM由甲硫氨酸循环产生，是一种对细胞代谢至关重要的天然锍化合物。INMT的表达在许多肿瘤组织中下调，可能促进肿瘤侵袭和转移。然而，INMT在头颈部鳞状细胞癌（HNSC）中的表达及其与甲基化和免疫浸润的关系仍是未知的。因此，我们首次评估了其表达、临床病理特征、预后、几条关键通路、DNA甲基化和免疫细胞浸润情况。利用多个肿瘤相关生物信息学数据库分析INMT表达的临床病理特征。此外，分析INMT表达在预后中的作用。在LinkedOmics网站上富集了几条与INMT相关的通路。另外，我们通过使用多个甲基化数据库详细分析了HNSC中INMT的甲基化情况。最后，用单样本基因集富集分析（ssGSEA）、Timer和TISIDB分析INMT基因表达与免疫浸润的关系。在HNSC中，mRNA和蛋白水平显著低于正常组织。INMT低表达与T分期、组织学分级、性别、吸烟史和饮酒情况具有统计学相关性。与INMT高表达的HNSC患者相比，INMT低表达的患者总生存期（OS）较差。此外，多因素分析显示INMT表达是HNSC患者预后的显著独立预测指标。基因富集分析表明，几条通路在INMT中富集，包括Ras信号通路、环鸟苷酸 - 蛋白激酶G（cGMP - PKG）信号通路等。此外，在多个甲基化数据库中检测到的INMT甲基化模式与mRNA表达和预后密切相关。最后，INMT与免疫浸润水平显著相关。INMT水平低的HNSC表现出较差的生存率、低甲基化和免疫浸润。对于HNSC，本研究表明INMT既是预后不良的生物标志物，也是免疫治疗的靶点。
