Prognostic and clinicopathological value of m6A regulators in human cancers: a meta-analysis

Abstract

Background: N6-methyladenosine (m6A) is the most abundant epigenetic modification. Although the dysregulation of m6A regulators has been associated with cancer progression in several studies, its relationship with cancer prognosis and clinicopathology is still controversial. Therefore, we evaluated the prognostic and clinicopathological value of m6A regulators in cancers by performing a comprehensive meta-analysis. Methods: The PubMed, Cochrane Library, Web of Science, and Embase databases were searched up to April 2022. Hazard ratios were used to analyze the association between m6A with prognosis. We also analyze the relationship between m6A and clinicopathology using odds ratios. Results: METTL3 overexpression predicted poor overall survival and disease-free survival in cancer patients (p < 0.001) such as gastric cancer (p < 0.001), esophageal squamous cell carcinoma (p < 0.001), oral squamous cell carcinoma (p = 0.002) and so on. Additionally, METTL3 overexpression was associated with poor pT stage (p < 0.001), pN stage (p < 0.001), TNM stage (p < 0.001), tumor size >5 cm (p < 0.001) and vascular invasion (p = 0.024). Conversely, METTL14 overexpression was positively associated with better OS (p < 0.001), negatively with poor pT stage (p = 0.001), pM stage (p = 0.002), pN stage (p = 0.011) and TNM stage (p < 0.001). Moreover, KIAA1429 overexpression was associated with poor OS (p = 0.001). YTHDF1 overexpression was also associated with advanced pM stage (p < 0.001) and tumor size >5 cm (p < 0.001). However, ALKBH5 overexpression was negatively associated with vascular invasion (p = 0.032). Conclusions: High expression of METTL3 predicted poor outcome. In contrast, high expression of METTL14 was associated with better outcome. Thus, we suggest that among all the m6A regulators, METTL3 and METTL14 could be potential prognostic markers in cancers.

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

“…High levels of METTL3 can predict poor overall survival (OS) and progression-free survival (PFS) in cancer patients, such as those with gastric cancer, ESOC, OSCC ( p = 0.002), and other cancers [ 168 ]. Conversely, high levels of METTL14 were positively associated with better OS.…”

“…Conversely, high levels of METTL14 were positively associated with better OS. High levels of KIAA1429 could predict poor OS ( p = 0.001), and high levels of ALKBH5 were negatively associated with vascular invasion ( p = 0.032) [ 168 ]. Thus, m6A regulators can predict the and PFS of various cancer patients.…”