Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome
Junhao Yin,
Jiayao Fu,
Jiabao Xu,
Changyu Chen,
Hanyi Zhu,
Baoli Wang,
Chuangqi Yu,
Xiujuan Yang,
Ruiyu Cai,
Mengyang Li,
Kaihan Ji,
Wanning Wu,
Yijie Zhao,
Zhanglong Zheng,
Yiping Pu,
Lingyan Zheng
Affiliations
Junhao Yin
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Jiayao Fu
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Jiabao Xu
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Changyu Chen
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Hanyi Zhu
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Baoli Wang
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Chuangqi Yu
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Xiujuan Yang
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China
Ruiyu Cai
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Mengyang Li
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Kaihan Ji
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Wanning Wu
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China
Yijie Zhao
Department of Oral and Maxillofacial Surgery, Shanghai Stomatological Hospital, Fudan University, 1258 Fuxin Zhong Road, Shanghai 200031, China
Zhanglong Zheng
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China
Yiping Pu
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China; Corresponding author. Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China.
Lingyan Zheng
Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China; National Center for Stomatology & National Clinical Research Center for Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Institute of Stomatology, Shanghai, China; Corresponding author. Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of stomatology, Shanghai Jiao Tong University, Shanghai, China.
The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.
