Comprehensive of N1-Methyladenosine Modifications Patterns and Immunological Characteristics in Ovarian Cancer

• Published in: Frontiers in immunology Vol. 12; p. 746647
• Main Authors: Liu, Jinhui, Chen, Can, Wang, Yichun, Qian, Cheng, Wei, Junting, Xing, Yan, Bai, Jianling
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.10.2021
• Subjects: Adenosine - metabolism; Carcinoma, Ovarian Epithelial - immunology; Carcinoma, Ovarian Epithelial - metabolism; Female; Humans; immune checkpoint blockade; Immunology; m1A modification; Methylation; ovarian cancer; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; prognosis; RNA Processing, Post-Transcriptional - immunology; tumor microenvironment; Tumor Microenvironment - immunology; m1A modification; tumor microenvironment; ovarian cancer; prognosis; immune checkpoint blockade
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.746647

recently, many researches have concentrated on the relevance between N1-methyladenosine (m1A) methylation modifications and tumor progression and prognosis. However, it remains unknown whether m1A modification has an effect in the prognosis of ovarian cancer (OC) and its immune infiltration. Based on 10 m1A modulators, we comprehensively assessed m1A modification patterns in 474 OC patients and linked them to TME immune infiltration characteristics. m1Ascore computed with principal component analysis algorithm was applied to quantify m1A modification pattern in OC patients. m1A regulators protein and mRNA expression were respectively obtained by HPA website and RT-PCR in clinical OC and normal samples. We finally identified three different m1A modification patterns. The immune infiltration features of these m1A modification patterns correspond to three tumor immune phenotypes, including immune-desert, immune-inflamed and immune-excluded phenotypes. The results demonstrate individual tumor m1A modification patterns can predict patient survival, stage and grade. The m1Ascore was calculated to quantify individual OC patient's m1A modification pattern. A high m1Ascore is usually accompanied by a better survival advantage and a lower mutational load. Research on m1Ascore in the treatment of OC patients showed that patients with high m1Ascore showed marked therapeutic benefits and clinical outcomes in terms of chemotherapy and immunotherapy. Lastly, we obtained four small molecule drugs that may potentially ameliorate prognosis. This research demonstrates that m1A methylation modification makes an essential function in the prognosis of OC and in shaping the immune microenvironment. Comprehensive evaluation of m1A modifications improves our knowledge of immune infiltration profile and provides a more efficient individualized immunotherapy strategy for OC patients.