m6A RNA Methylation Regulators Impact Prognosis and Tumor Microenvironment in Renal Papillary Cell Carcinoma

Lianze Chen; Baohui Hu; Xinyue Song; Lin Wang; Mingyi Ju; Zinan Li; Chenyi Zhou; Ming Zhang; Qian Wei; Qiutong Guan; Longyang Jiang; Ting Chen; Minjie Wei; Lin Zhao

doi:10.3389/fonc.2021.598017

m⁶A RNA Methylation Regulators Impact Prognosis and Tumor Microenvironment in Renal Papillary Cell Carcinoma

Front Oncol. 2021 Mar 16:11:598017. doi: 10.3389/fonc.2021.598017. eCollection 2021.

Authors

Lianze Chen^{1

2}, Baohui Hu^{1

2}, Xinyue Song^{1

2}, Lin Wang^{1

2}, Mingyi Ju^{1

2}, Zinan Li^{1

2}, Chenyi Zhou^{1

2}, Ming Zhang^{1

2}, Qian Wei^{1

2}, Qiutong Guan^{1

2}, Longyang Jiang^{1

2}, Ting Chen^{1

2}, Minjie Wei^{1

2

3}, Lin Zhao^{1

2}

Affiliations

¹ Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
² Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.
³ Liaoning Medical Diagnosis and Treatment Center, Shenyang, China.

Abstract

Accumulating evidence has proven that N6-methyladenosine (m⁶A) RNA methylation plays an essential role in tumorigenesis. However, the significance of m⁶A RNA methylation modulators in the malignant progression of papillary renal cell carcinoma (PRCC) and their impact on prognosis has not been fully analyzed. The present research set out to explore the roles of 17 m⁶A RNA methylation regulators in tumor microenvironment (TME) of PRCC and identify the prognostic values of m⁶A RNA methylation regulators in patients afflicted by PRCC. We investigated the different expression patterns of the m⁶A RNA methylation regulators between PRCC tumor samples and normal tissues, and systematically explored the association of the expression patterns of these genes with TME cell-infiltrating characteristics. Additionally, we used LASSO regression to construct a risk signature based upon the m⁶A RNA methylation modulators. Two-gene prognostic risk model including IGF2BP3 and HNRNPC was constructed and could predict overall survival (OS) of PRCC patients from the Cancer Genome Atlas (TCGA) dataset. The prognostic signature-based risk score was identified as an independent prognostic indicator in Cox regression analysis. Moreover, we predicted the three most significant small molecule drugs that potentially inhibit PRCC. Taken together, our study revealed that m⁶A RNA methylation regulators might play a significant role in the initiation and progression of PRCC. The results might provide novel insight into exploration of m⁶A RNA modification in PRCC and provide essential guidance for therapeutic strategies.

Keywords: epigenetic modification; m6A RNA methylation; prognostic signature; renal papillary cell carcinoma; tumor microenvironment.