Research Paper Volume 12, Issue 17 pp 17022—17037
Retrospective study of gene signatures and prognostic value of m6A regulatory factor in non-small cell lung cancer using TCGA database and the verification of FTO
- 1 Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- 2 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Received: March 14, 2020 Accepted: June 19, 2020 Published: September 9, 2020https://doi.org/10.18632/aging.103622
How to Cite
Copyright: © 2020 Shi 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.
N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA. However, little is known about its role in non-small cell lung cancer (NSCLC). In this study, a total of 1017 NSCLC patients from the cancer genome atlas (TCGA) database with copy number variation (CNV) data were included. Log-rank tests and Cox regression model were used for survival analysis. The relationship between m6A regulators and clinicopathological features was evaluated using the chi-square test. The alteration of m6A regulators were related to T stage. Patients with any CNVs of regulators genes had worse overall survival (OS) than those with diploid genes. The deletion of m6A writer genes was an independent risk factor for poor OS, and the effect synergized with that of copy number gain of eraser genes. High expression of Fat mass-and obesity-associated gene (FTO) was associated with KRAS signaling up. Knockdown of FTO increased m6A content and inhibit proliferation of A549 lung cancer cell. Thus, we identified the genetic changes of m6A regulatory factors in NSCLC for the first time and found a significant relationship between these changes and poor clinical characteristics. FTO might play an important role in promoting NSCLC by decreasing m6A level and activating KRAS signaling.