The YTH Domain Family of N6-Methyladenosine “Readers” in the Diagnosis and Prognosis of Colonic Adenocarcinoma

Abstract

To profile the landscape of methylation N6 adenosine (m6A) RNA regulators in colonic adenocarcinoma (COAD) and to explore potential diagnostic and prognostic biomarkers, we assessed the differential expression patterns of m6A RNA methylation regulators between 418 COAD patients and 41 controls based on profiling from The Cancer Genome Atlas (TCGA) database. We plotted the receiver operating characteristic (ROC) curves and calculated the area under the curve (AUC) values to estimate the discrimination ability. The relationship between the expression of m6A RNA methylation regulators and clinicopathological characteristics was explored. Kaplan-Meier plotter, log-rank test, and Cox regression were used and a nomogram was created to explore the prognostic significance of m6A-related genes in overall survival at the mRNA level. Pathway analysis was performed by gene set enrichment analysis (GSEA) using TCGA dataset, and a coexpression network was built based on the STRING database. We observed that YTHDF1, METTL3, and KIAA1429 were significantly upregulated, while YTHDF3, YTHDC2, METTL14, and ALKBH5 were significantly downregulated in COAD samples compared to normal samples. YTHDF1 had the highest diagnostic value. Low expression of YTHDF3 predicted a poor survival rate in COAD patients. YTHDC2 was related to sex and showed a downward trend as clinical stage increased. Our results indicate that the YT521-B homology (YTH) domain family (“readers”), especially YTHDF1, YTHDF3, and YTHDC2, might play a significant role in the detection, progression, and prognosis of COAD, indicating that they are promising cancer biomarkers.

Identification of m6A-Related Biomarkers Associated with Prognosis of Colorectal Cancer

“…Previous study about CRC and m6A methylation focused on m6A regulators [ 32 ], one subtype of CRC, such as COAD [ 33 ], or the comparison of tumor and normal tissues [ 34 ]. In the study, we systematically analyzed RNA sequencing data of CRC (including COAD and READ) patients from TCGA and GEO database.…”

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

“…According to the different CRC cohorts, ALKBH5 is low expression in CRC patients at mRNA and protein levels, playing a suppressor gene role in CRC. [61][62][63][64] Besides, the expression of ALKBH5 is significantly associated with age, stage, invasion and metastasis, overall survival and disease-free survival, which is also verified by experiments in vitro and in vivo. 64 However, some scholars argue that ALKBH5 is upregulated in CRC tissues and cells.…”

Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma

“…Studies have shown that YTHDC2 can specifically recognize and bind m6A through the YTH sequence, promote mRNA translation and affect mRNA stability (4). The YTHDC2 gene is essential for the maintenance of meiosis and the production of germ cells (23)(24)(25), and is involved in the occurrence and development of a variety of diseases, including autism, pancreatic cancer, colon adenocarcinoma, liver cancer, and lung adenocarcinoma (26)(27)(28)(29)(30). The HNRNPA2B1 gene was highly expressed in a variety of human cancers, such as prostate cancer (31), pancreatic cancer (32), and hepatocellular carcinoma (33).…”