Zhu Chong-Ying, Yang Qi-Wei, Mu Xin-Yue, Zhai Yan-Yu, Zhao Wen-Yan, Yin Zuo-Jing
Department of Gynecology and Obstetrics, Ruijin Hospital, Center for Single-Cell Omics, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Depanrtment of Urology, The Third Affiliated Hospital of Naval Military Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, China.
Cancer Inform. 2024 Nov 16;23:11769351241300030. doi: 10.1177/11769351241300030. eCollection 2024.
Emerging evidence suggests that N6-methyladenosine (mA) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential role of mA methylation "readers" in regulation of cancer prognosis at the pan-cancer level.
Herein, we focused on one special protein family of the "readers" of mA methylation, YT521-B homology (YTH) domain family genes, which were observed to be frequently dysregulated in tumor tissues and closely associated with cancer prognosis. Then, a comprehensive analysis of modulation in cancer prognosis was conducted by integrating RNA sequencing (RNAseq) datasets of YTH family genes and clinical information at the pan-cancer level.
YTH family genes were significantly differentially expressed in most of the cancers, particularly increased in Gastrointestinal cancers, and decreased in Endocrine and Urologic cancers. In addition, they were observed to be associated with overall survival (OS) and disease-specific survival (DSS) with various extent, especially in lower grade glioma (LGG), thyroid cancer (THCA), liver hepatocellular carcinoma (LIHC) and kidney clear cell carcinoma (KIRC), so were some "writers" (METLL3, METLL14, WTAP) and "erasers" (FTO, ALKBH5). Further survival analysis illustrated that YTH family genes specifically YTHScore constructed by combining 5 YTH family genes, as well as RWEScore calculated by combining genes from "readers"-"writers"-"erasers" could dramatically distinguish tumor prognosis in 4 representative cancers. As expected, YTHScore presented an equally comparable prognostic classification with RWEScore. Finally, analysis of immune signatures and clinical characteristics implied that, the activity of the innate immune, diagnostic age, clinical stage, Tumor-Node-Metastasis (TNM) stage and immune types, might play specific roles in modulating tumor prognosis.
The study demonstrated that YTH family genes had the potential to predict tumor prognosis, in which the YTHScore illustrated equal ability to predict tumor prognosis compared to RWEScore, thus providing insights into prognostic biomarkers and therapeutic targets at the pan-cancer level.
新出现的证据表明，N6-甲基腺苷（m⁶A）甲基化通过多种机制在癌症中发挥关键作用。这项工作旨在揭示m⁶A甲基化“读取器”在泛癌水平上对癌症预后调控中的重要作用。
在此，我们聚焦于m⁶A甲基化“读取器”的一个特殊蛋白家族，即YT521-B同源（YTH）结构域家族基因，观察到其在肿瘤组织中经常失调且与癌症预后密切相关。然后，通过整合泛癌水平上YTH家族基因的RNA测序（RNAseq）数据集和临床信息，对癌症预后的调控进行了综合分析。
YTH家族基因在大多数癌症中显著差异表达，在胃肠道癌症中尤其上调，而在内分泌和泌尿系统癌症中下调。此外，观察到它们在不同程度上与总生存期（OS）和疾病特异性生存期（DSS）相关，特别是在低级别胶质瘤（LGG）、甲状腺癌（THCA）、肝细胞肝癌（LIHC）和肾透明细胞癌（KIRC）中，一些“写入器”（METTL3、METTL14、WTAP）和“擦除器”（FTO、ALKBH5）也是如此。进一步的生存分析表明，YTH家族基因，特别是通过组合5个YTH家族基因构建的YTHScore，以及通过组合“读取器”-“写入器”-“擦除器”中的基因计算出的RWEScore，可以显著区分4种代表性癌症中的肿瘤预后。正如预期的那样，YTHScore与RWEScore具有同样可比的预后分类。最后，对免疫特征和临床特征的分析表明，先天免疫活性、诊断年龄、临床分期、肿瘤-淋巴结-转移（TNM）分期和免疫类型可能在调节肿瘤预后中发挥特定作用。
该研究表明，YTH家族基因具有预测肿瘤预后的潜力，其中YTHScore显示出与RWEScore同等的预测肿瘤预后的能力，从而为泛癌水平上的预后生物标志物和治疗靶点提供了见解。
