Comprehensive Analysis of 5-Methylcytosine (m5C) Regulators and the Immune Microenvironment in Pancreatic Adenocarcinoma to Aid Immunotherapy

Ronglin Wang; Yongdong Guo; Peixiang Ma; Yang Song; Jie Min; Ting Zhao; Lei Hua; Chao Zhang; Cheng Yang; Jingjie Shi; Liaoliao Zhu; Dongxue Gan; Shanshan Li; Junqiang Li; Haichuan Su

doi:10.3389/fonc.2022.851766

Comprehensive Analysis of 5-Methylcytosine (m⁵C) Regulators and the Immune Microenvironment in Pancreatic Adenocarcinoma to Aid Immunotherapy

Front Oncol. 2022 Mar 31:12:851766. doi: 10.3389/fonc.2022.851766. eCollection 2022.

Authors

Ronglin Wang¹, Yongdong Guo¹, Peixiang Ma¹, Yang Song¹, Jie Min¹, Ting Zhao¹, Lei Hua¹, Chao Zhang¹, Cheng Yang¹, Jingjie Shi¹, Liaoliao Zhu¹, Dongxue Gan¹, Shanshan Li¹, Junqiang Li¹, Haichuan Su¹

Affiliation

¹ Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, China.

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers and has a poor prognosis. As a critical RNA modification, 5-methylcytosine (m⁵C) has been reported to regulate tumor progression, including PAAD progression. However, a comprehensive analysis of m⁵C regulators in PAAD is lacking.

Methods: In the present study, PAAD datasets were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and ArrayExpress databases. The expression pattern of m⁵C regulators were analyzed and patients were divided into different m⁵C clusters according to consensus clustering based on m⁵C regulators. Additionally, m⁵C differentially expressed genes (DEGs) were determined using Limma package. Based on m⁵C DEGs, patients were divided into m⁵C gene clusters. Moreover, m⁵C gene signatures were derived from m⁵C DEGs and a quantitative indicator, the m⁵C score, was developed from the m⁵C gene signatures.

Results: Our study showed that m⁵C regulators were differentially expressed in patients with PAAD. The m⁵C clusters and gene clusters based on m⁵C regulators and m⁵C DEGs were related to immune cell infiltration, immune-related genes and patient survival status, indicating that m⁵C modification play a central role in regulating PAAD development partly by modulating immune microenvironment. Additionally, a quantitative indicator, the m⁵C score, was also developed and was related to a series of immune-related indicators. Moreover, the m⁵C score precisely predicted the immunotherapy response and prognosis of patients with PAAD.

Conclusion: In summary, we confirmed that m⁵C regulators regulate PAAD development by modulating the immune microenvironment. In addition, a quantitative indicator, the m⁵C score, was developed to predict immunotherapy response and prognosis and assisted in identifying PAAD patients suitable for tailored immunotherapy strategies.

Keywords: RNA modification; immune microenvironment; immunotherapy; m5C regulators; pancreatic adenocarcinoma.