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The pathological tissue expression pattern and clinical significance of m6A-regulatory genes in non-small cell lung

Yujie Li1,2, Xin Zhang3,4,5, Junchao Cai6,7

  • 1Department of Pulmonary and Critical Care Medicine, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, China.

The Journal of Gene Medicine
|November 9, 2021
PubMed
Abstract

Insights

Aberrant expression of key m6A regulators like METTL3, ALKBH5, YTHDC2, and YTHDF1 is linked to non-small cell lung cancer (NSCLC) progression. These proteins may serve as crucial biomarkers for early NSCLC detection and diagnosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Aberrant expression of m6A-related proteins is implicated in non-small cell lung cancer (NSCLC) development and progression.
  • Existing research often focuses on single m6A regulators, leaving the comprehensive expression patterns of multiple m6A regulatory proteins in NSCLC largely uncharacterized.
  • Systematic investigation of these proteins in clinical NSCLC specimens is crucial.

Purpose of the Study:

  • To systematically analyze the expression of multiple m6A regulatory proteins in NSCLC.
  • To investigate the correlation between m6A regulatory protein expression and clinicopathological features, patient survival, and common gene mutations (TP53, EGFR, KRAS) in NSCLC.
  • To identify potential m6A-related biomarkers for NSCLC.

Main Methods:

  • Bioinformatic analysis of mRNA levels for 13 core m6A regulators using The Cancer Genome Atlas (TCGA) and AE-meta databases.
  • Immunohistochemistry to assess protein expression of m6A regulators in 61 benign lung tissues and 316 NSCLC tissues.
  • Statistical analysis to correlate protein expression with clinicopathological data, survival outcomes, and gene mutations.

Main Results:

  • Upregulated mRNA levels of YTHDF1 were observed in NSCLC.
  • Immunohistochemistry confirmed significant upregulation of METTL3, ALKBH5, YTHDC2, and YTHDF1 protein expression in NSCLC tissues.
  • Positive correlations were found between elevated METTL3, ALKBH5, YTHDC2, and YTHDF1 expression and poorer clinicopathological features and survival in NSCLC patients.
  • Higher METTL3 protein levels were associated with EGFR exon-19 mutations in NSCLC patients.

Conclusions:

  • METTL3, ALKBH5, YTHDC2, and YTHDF1 are significantly dysregulated in NSCLC.
  • These m6A regulators demonstrate potential as predictive biomarkers for NSCLC.
  • Findings support the utility of these proteins for facilitating early NSCLC detection and diagnosis.
Keywords:
NSCLCbioinformaticsimmunohistochemistrym6A regulatory protein

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