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Detecting the Tumor Prognostic Factors From the YTH Domain Family Through Integrative Pan-Cancer Analysis
Chong-Ying Zhu1, Qi-Wei Yang2,3, Xin-Yue Mu4
1Department of Gynecology and Obstetrics, Ruijin Hospital, Center for Single-Cell Omics, School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Objectives:
Emerging evidence suggests that N6-methyladenosine (m6A) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential role of m6A methylation "readers" in regulation of cancer prognosis at the pan-cancer level.
Methods:
Herein, we focused on one special protein family of the "readers" of m6A 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.
Results:
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.
Conclusions:
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.
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