Ding Yezhou, Feng Mingyang, Chi Wanqing, Wang Xiaoyin, An Baoyan, Liu Kehui, Lou Shike, Wang Xiaolin, Wang Hui
Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 20025, China.
Epidemiology of Microbial Diseases Department, Yale University School of Public Health, New Haven, Connecticut, CT, USA.
Cancer Cell Int. 2025 Jan 17;25(1):15. doi: 10.1186/s12935-024-03616-7.
Methyltransferase-like (METTL) family protein plays a crucial role in the progression of malignancies. However, the function of METTL17 across pan-cancers, especially in hepatocellular carcinoma (HCC) is still poorly understood.
All original data were downloaded from TCGA, GTEx, HPA, UCSC databases and various data portals. First, we comprehensively analyzed RNA-seq data from the HPA database of 25 human tissues. An array of bioinformatics methods was employed to explore the potential oncogenic roles of METTL17, including analyzing its related prognosis, mutation, landscapes, tumor stemness index, immune cell infiltration, and other factors among different tumors. Additionally, gene set enrichment analysis (GSEA) was used to analyze pathways associated with METTL17 in HCC. Immunohistochemistry (IHC) was performed on clinical samples to validate the differential expression of METTL17 in HCC and normal tissues. Ultimately, we constructed a METTL17-related risk-score model of HCC and validated its prognostic classification efficiency. Survival rates were calculated using the Kaplan-Meier method. Statistical significance was defined as P < 0.05.
METTL17 was differentially expressed in various cancers. METTL17 maintained strong correlations with the cancer patient's prognosis, genetic alterations, tumor stemness index, and immune-infiltrated cells, etc. In addition, IHC experiments verified that METTL expression was significantly decreased in liver tissues of HCC patients compared to normal liver tissue. GESA analysis indicated METTL17 mainly involves oncogenic and immune-related pathways among HCC. MRPS5, CHCHD2, NCBP1, LRPPRC, DAP3, and BMS1 were included in a prognostic model based on METTL17's interaction networks. Kaplan-Meier survival analysis of the prognostic model showed that the overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (P < 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) of the 1-year, 3-year, and 5-year OS were 0.747, 0.671, and 0.631, respectively.
METTL17 may serve as a novel prognostic marker and therapeutic target for human tumors, offering a theoretical foundation for formulating more effective and tailored clinical treatment options for cancers, particularly HCC.
甲基转移酶样（METTL）家族蛋白在恶性肿瘤进展中起关键作用。然而，METTL17在泛癌中的功能，尤其是在肝细胞癌（HCC）中的功能仍知之甚少。
所有原始数据均从TCGA、GTEx、HPA、UCSC数据库及各种数据门户下载。首先，我们全面分析了来自HPA数据库的25种人体组织的RNA测序数据。采用一系列生物信息学方法探索METTL17的潜在致癌作用，包括分析其相关预后、突变、图谱、肿瘤干性指数、免疫细胞浸润以及不同肿瘤中的其他因素。此外，基因集富集分析（GSEA）用于分析HCC中与METTL17相关的通路。对临床样本进行免疫组织化学（IHC）以验证METTL17在HCC和正常组织中的差异表达。最终，我们构建了HCC的METTL17相关风险评分模型并验证其预后分类效率。使用Kaplan-Meier方法计算生存率。统计学显著性定义为P < 0.05。
METTL17在多种癌症中差异表达。METTL17与癌症患者的预后、基因改变、肿瘤干性指数和免疫浸润细胞等保持密切相关性。此外，IHC实验证实，与正常肝组织相比，HCC患者肝组织中METTL表达显著降低。GESA分析表明，METTL17在HCC中主要涉及致癌和免疫相关通路。基于METTL17的相互作用网络，MRPS5、CHCHD2、NCBP1、LRPPRC、DAP3和BMS1被纳入预后模型。预后模型的Kaplan-Meier生存分析表明，低风险组的总生存期（OS）明显优于高风险组（P < 0.001）。1年、3年和5年OS的受试者工作特征（ROC）曲线下面积（AUC）分别为0.747、0.671和0.631。
METTL17可能作为人类肿瘤的一种新型预后标志物和治疗靶点，为制定更有效、更具针对性的癌症临床治疗方案，尤其是HCC的治疗方案提供理论基础。
