The Sex Differences in Uveal Melanoma: Potential Roles of EIF1AX, Immune Response and Redox Regulation
Autor: | Phillip Winston Miller, Evan S. Glazer, Chi-Yang Chiu, Daniel L. Johnson, Zhao-Hui Wu, Matthew W. Wilson, Feng Liu-Smith |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Uveal Neoplasms medicine.disease_cause immune response genomics analysis 0302 clinical medicine Gene expression Copy-number variation Melanoma RC254-282 Cancer Sex Characteristics epidemi-ology Incidence (epidemiology) Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030220 oncology & carcinogenesis EIF1AX Female uveal melanoma Oxidation-Reduction Biotechnology medicine.medical_specialty DNA Copy Number Variations sex difference Oncology and Carcinogenesis Article redox regulation 03 medical and health sciences Immune system Rare Diseases Internal medicine medicine Genetics Humans Oncology & Carcinogenesis Gene Aged business.industry Prevention Human Genome Immunity medicine.disease 030104 developmental biology Endocrinology Mutation Carcinogenesis business |
Zdroj: | Current Oncology, Vol 28, Iss 245, Pp 2801-2811 (2021) Current Oncology Volume 28 Issue 4 Pages 245-2811 Current oncology (Toronto, Ont.), vol 28, iss 4 |
ISSN: | 1198-0052 1718-7729 |
Popis: | Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM. |
Databáze: | OpenAIRE |
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