RNA-Binding Protein IGF2BP1 Associated With Prognosis and Immunotherapy Response in Lung Adenocarcinoma.

Jinfeng Liu,Iokfai Cheang,Jinghang Li,Zhi Li,Chunlei Zhou

doi:10.3389/fgene.2022.777399

Abstract

N6-methyladenosine (m6A) is the most common modification in eukaryotic RNAs and plays a vital role in the tumorigenesis and metastasis of various cancers. However, a comprehensive study of m6A methylation regulators in lung adenocarcinoma (LUAD) is still lacking. The present study aimed to systematically explore the role of m6A methylation regulators in LUAD. RNA sequencing data of 20 m6A methylation regulators and clinical data of LUAD patients were downloaded from The Cancer Genome Atlas (TCGA) database. The prognosis value of m6A methylation regulators in LUAD was evaluated using the Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan database. The correlation between IGF2BP1 and immune infiltrates in LUAD was investigated via CIBERSORT and Tumor Immune Estimation Resource (TIMER). A total of 15 m6A modification regulators were significantly abnormally expressed in LUAD tissues. Survival analysis revealed that four genes (HNRNPC, HNRNPA2B1, IGF2BP1, and IGF2BP3) were significantly associated with poor prognosis in LUAD. Multivariate Cox regression analysis showed that only IGF2BP1 was an independent predictor of LUAD after adjusting common clinical parameters. The mutation rates of m6A modification regulators in LUAD were less than 10%. Further analysis revealed that IGF2BP1 expression was significantly correlated with immune infiltration, the expression of immune checkpoints, and tumor mutational burden (TMB) in LUAD. Our findings suggest that IGF2BP1 is an independent predictor and related to immunotherapy response in LUAD, which maybe a potential novel biomarker for LUAD prognosis and the status of tumor immunity.

Highlights

Lung cancer is one of the most common malignancies worldwide
To explore the role of m6A modification regulators in lung adenocarcinoma (LUAD) tumorigenesis, we systematically analyzed the expression patterns of 20 m6A modification regulators in LUAD tumor and normal lung tissues based on The Cancer Genome Atlas (TCGA) database
Compared with the normal tissues, the expressions of HNRNPA2B1, HNRNPC, IGF2BP1, IGF2BP3, RBMX, YTHDF1, YTHDF2, METL3, RBM15, and VIRMA were upregulated in LUAD tissues, while the expressions of ALKBH5, FTO, METL14, WTAP, and ZC3H13 were downregulated in LUAD tissues (Figure 2)

Summary

Introduction

Lung cancer is one of the most common malignancies worldwide. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. The development of lung cancer is the result of the combined effect of genetic and environmental factors. N6-methyladenosine (m6A) is the most prevalent and abundant transcriptional modification in eukaryotic RNAs and plays a key role in the process of cell self-renewal and differentiation m6A Methylation Regulators and LUAD (Desrosiers et al, 1974). The m6A modification is highly conservative, which is commonly found in 3’untranslated region (UTR), protein coding sequences (CDS), and transcription starting site (TSS). It regulates the posttranscriptional level of mRNA without changing the base sequence (Niu et al, 2013). The abnormality of m6A modification can lead to the occurrence of many human diseases, such as tumors, metabolic diseases, and neurological diseases (He et al, 2019; Zhang et al, 2021)

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