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
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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