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Prognostic signature and immune efficacy of m1A-, m5C- and m6A-related regulators in cutaneous melanoma
Authors:Xian rui Wu  Zheng Chen  Yang Liu  Zi zi Chen  Fengjie Tang  Zhi zhao Chen  Jing jing Li  Jun lin Liao  Ke Cao  Xiang Chen  Jianda Zhou
Institution:1. Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China;2. Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China

Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Software (equal), Visualization (equal), Writing - original draft (equal);3. Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, Hunan, China

Contribution: Formal analysis (equal), ?Investigation (equal), Software (equal), Visualization (equal);4. Department of Plastic Surgery of Xiangya Hospital, Central South University, Changsha, Hunan, China

Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Validation (equal);5. Departments of Medical Cosmetology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, China

Contribution: Data curation (equal), Formal analysis (equal), Methodology (equal), Visualization (equal);6. Department of Oncology of Third Xiangya Hospital, Central South University, Changsha, Hunan, China

Contribution: Data curation (equal), Methodology (equal), Project administration (equal), Supervision (equal), Validation (equal), Writing - review & editing (equal);7. Department of Dermatology, The Xiangya Hospital, Central South University, Changsha, Hunan, China

Contribution: Conceptualization (equal), Data curation (equal), Methodology (equal), Project administration (equal), Resources (equal), Supervision (equal)

Abstract:Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N6-methyladenosine (m6A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1A-, m5C- and m6A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1A-, m5C- and m6A-related regulators may also be promising biomarkers for future research.
Keywords:cutaneous melanoma  immunotherapy  m1A  m5C  m6A  prognosis  tumour microenvironment
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