Prognostic Significance and Tumor Immune Microenvironment Heterogenicity of m5C RNA Methylation Regulators in Triple-Negative Breast Cancer

Zhidong Huang; Junfan Pan; Helin Wang; Xianqiang Du; Yusheng Xu; Zhitang Wang; Debo Chen

doi:10.3389/fcell.2021.657547

Prognostic Significance and Tumor Immune Microenvironment Heterogenicity of m5C RNA Methylation Regulators in Triple-Negative Breast Cancer

Front Cell Dev Biol. 2021 Apr 13:9:657547. doi: 10.3389/fcell.2021.657547. eCollection 2021.

Authors

Zhidong Huang¹, Junfan Pan², Helin Wang¹, Xianqiang Du¹, Yusheng Xu¹, Zhitang Wang¹, Debo Chen¹

Affiliations

¹ Quanzhou First Hospital of Fujian Medical University, Quanzhou, China.
² Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Abstract

Purpose: The m5C RNA methylation regulators are closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the gene expression, clinicopathological characteristics, and prognostic value of m5C regulators in triple-negative breast cancer (TNBC) and their correlation with the tumor immune microenvironment (TIM).

Methods: The TNBC data, Luminal BC data and HER2 positive BC data set were obtained from The Cancer Genome Atlas and Gene Expression Omnibus, and 11 m5C RNA methylation regulators were analyzed. Univariate Cox regression and the least absolute shrinkage and selection operator regression models were used to develop a prognostic risk signature. The UALCAN and cBioportal databases were used to analyze the gene characteristics and gene alteration frequency of prognosis-related m5C RNA methylation regulators. Gene set enrichment analysis was used to analyze cellular pathways enriched by prognostic factors. The Tumor Immune Single Cell Hub (TISCH) and Timer online databases were used to explore the relationship between prognosis-related genes and the TIM.

Results: Most of the 11 m5C RNA methylation regulators were differentially expressed in TNBC and normal samples. The prognostic risk signature showed good reliability and an independent prognostic value. Prognosis-related gene mutations were mainly amplified. Concurrently, the NOP2/Sun domain family member 2 (NSUN2) upregulation was closely related to spliceosome, RNA degradation, cell cycle signaling pathways, and RNA polymerase. Meanwhile, NSUN6 downregulation was related to extracellular matrix receptor interaction, metabolism, and cell adhesion. Analysis of the TISCH and Timer databases showed that prognosis-related genes affected the TIM, and the subtypes of immune-infiltrating cells differed between NSUN2 and NSUN6.

Conclusion: Regulatory factors of m5C RNA methylation can predict the clinical prognostic risk of TNBC patients and affect tumor development and the TIM. Thus, they have the potential to be a novel prognostic marker of TNBC, providing clues for understanding the RNA epigenetic modification of TNBC.

Keywords: NSUN2; NSUN6 prognostic risk signature; m5C RNA methylation regulator; triple-negative breast cancer; tumor immune microenvironment.