Abstract
Backgroundrecently, 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.MethodsBased 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.ResultsWe 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.ConclusionThis 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.
Highlights
Most scientists have focused on the critical effect on RNA methylation modifications in regulating genetic function
We found that some m1A regulators, including ALKBH1, ALKBH3, TRMT6, TRMT10C, YTHDF1 and YTHDF2 are oncogenic and that overexpression of these genes results in worse prognosis for OC patients
After applying ESTIMATE algorithm, we found that gene cluster-A has the most immune and matrix components in TME, followed by gene cluster-B (P
Summary
Most scientists have focused on the critical effect on RNA methylation modifications in regulating genetic function. Different from DNA methylation, RNA methylation modifications, including N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1methyladenosine (m1A), mainly regulate genetic expression at the post-transcriptional level [1,2,3,4]. M1A methylation modification maintains the structure and function of non-coding RNAs (ncRNAs), a process that is dynamically reversible and involves three classes of molecules: methyltransferases, demethylases and binding proteins [8]. The m1A binding proteins comprising YTHDF1, YTHDF2, YTHDF3 and YTHDC1 can read m1A methylation modification information and recognize and bind m1A methylation sites [16]. These regulatory genes make an essential function in the process of modifying m1A. More researches have shown that abnormal expression or mutations of m1A regulatory molecules can affect transcription and translation processes, leading to abnormal pathological processes such as abnormal cell proliferation, retarded organismal development and tumorigenesis [17,18,19,20]
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