Methylation Pattern Mediated by m6A Regulator and Tumor Microenvironment Invasion in Lung Adenocarcinoma.

Feng Jiang,Chuyan Wu,Ming Wang,Xiaoqin Liu,Yifang Hu,Alessandro Poggi

doi:10.1155/2022/2930310

Abstract

Background Recent research has established the existence of epigenetic modulation of the immune response. The possible involvement of RNA-n6-methyladenosine (m6A) alteration in tumor microenvironment (TME) cell invasion, on the other hand, is unknown. Methods Based on 23 m6A regulators, we examined the alteration patterns of m6A in 629 LUAD tissues and comprehensively connected these modification patterns with TME cell invasion characteristics. The m6A score was calculated, and the m6A modification pattern of a single tumor was quantified using principal component analysis. Then, we further verified the expression of m6A related enzymes and the role hub gene (NOL10) closely related to survival in lung cancer cell lines. Results Three separate m6A alteration modes have been discovered. TME cell invasion characteristics in the three modes were very similar to the three immunological phenotypes of tumors: immunological rejection, immunological inflammation, and immunological desert. We show that assessing the m6A modification pattern in a single tumor may help predict tumor inflammatory stage, subtype, TME interstitial activity, and prognosis. TME phenotypic inflammation is indicated by a high m6A score, which is characterized by elevated mutation load and immunological activation. The low m6A subtype showed matrix activation and ineffective immune infiltration, indicating that the TME phenotype of noninflammation and immunological rejection had a poor survival probability. Increased neoantigen burden was also linked to a high m6A score. Patients with a higher m6A score saw substantial therapeutic and clinical improvements. And reducing hub gene NOL10 expression substantially inhibited lung cancer cell growth and migration. Conclusions This research shows that m6A alteration is critical in the creation of TME variety and complexity. The analysis of a single tumor's m6A alteration pattern will aid in improving our knowledge of TME invasion features and guiding more effective immunotherapy tactics.

Highlights

Lung cancer is the most frequent kind of cancer in the world, with the greatest fatality rate [1, 2]
To analyze the m6A modification pattern of a single lung adenocarcinoma patient—m6A gene features, which we call m6A score—we developed a scoring method to quantify the m6A modification pattern of a single tumor
When it came to copying number variation (CNV), YTHDF1, VIRMA, and FMR1 had a high rate of amplification, but RMB15 and METTL16 were mostly copy number losses (Figure 2(b))

Summary

Introduction

Lung cancer is the most frequent kind of cancer in the world, with the greatest fatality rate [1, 2]. PD1/PDL1 immune checkpoint inhibitors have been developed and used in the treatment of lung adenocarcinoma [6, 7]. A flurry of studies has revealed that the microenvironment in which cancer cells develop and survive is critical to tumor progression and treatment [8]. TME cell invasion characteristics in the three modes were very similar to the three immunological phenotypes of tumors: immunological rejection, immunological inflammation, and immunological desert. The low m6A subtype showed matrix activation and ineffective immune infiltration, indicating that the TME phenotype of noninflammation and immunological rejection had a poor survival probability. The analysis of a single tumor’s m6A alteration pattern will aid in improving our knowledge of TME invasion features and guiding more effective immunotherapy tactics

Methods

Results

Conclusion