Research Paper Volume 14, Issue 21 pp 8818—8838

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

Zhangci Su1,2,3, *, , Leyao Xu1,2,3, *, , Xinning Dai1,2,3, *, , Mengyao Zhu1,2,3,4, , Xiaodan Chen1,2,3, , Yuanyuan Li1,2,3, , Jie Li1,2,3, , Ruihan Ge1,2,3, , Bin Cheng1,2,3, , Yun Wang2,3, ,

  • 1 Hospital of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China
  • 2 Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China
  • 3 Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, P.R. China
  • 4 Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, P.R. China
* Equal contribution

Received: August 25, 2022       Accepted: October 24, 2022       Published: November 7, 2022
How to Cite

Copyright: © 2022 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


METTL3: Methyltransferase Like 3; METTL14: Methyltransferase Like 14; METTL16: Methyltransferase Like 16; RBM15: RNA-binding protein 15; RBM15B: Putative RNA-binding protein 15B; HNRNPC: Heterogeneous nuclear ribonucleoproteins; HNRNPA2B1: Heterogeneous nuclear ribonucleoproteins A2/B1; YTHDF1: YTH domain-containing family protein 1; YTHDF2: YTH domain-containing family protein 2; YTHDF3: YTH domain-containing family protein 3; YTHDC1: YTH domain-containing protein 1; FTO: Alpha-ketoglutarate-dependent dioxygenase FTO; ALKBH5: RNA demethylase ALKBH5; OS: overall survival; DFS: disease-free survival; RFS: recurrence-free survival; HR: hazard ratio; OR: odds ratio; M/F: male/female; NA: not available; cut-off value: the value that can be diagnosed as positive/high expression of a m6A regulator; IHC: immunohistochemistry; IF: immunofluorescence; qRT-PCR: quantitative reverse transcription polymerase chain reaction; P: prospective; CI: confidence interval.