Expression of acyl-CoA synthetase medium-chain 3 is associated with obesity in melanoma patients and correlates with androgen receptor

Abstract

Background: Malignant melanoma is a typical type of cancer that feature the obesity paradox. Objectives: We aim to evaluate the role of acyl-CoA synthetase medium-chain 3 (ACSM3) in obesity paradox in malignant melanoma (MM). Methods: With reproduction of the Cancer Genome Atlas (TCGA) MM dataset and validation using immunohistochemistry, we evaluated correlations of ACSM3 expression with body mass index (BMI), gender, and androgen receptor (AR) expression. Results: ACSM family genes were downregulated in MM and in normal skin exposed to ultraviolet. Higher expression of ACSM3 was associated with improved overall survival in men but not in women. Subgroup analysis showed the best survival outcome in obese patients with high ACSM3 expression. ACSM3 expression was significantly lower in cases with ulceration. NET-GE-based gene enrichment analysis of ACSM-overexpressed cases showed significant enrichment in lipid metabolism and butanoate metabolism. AR stood as the top possible transcription factor of ACSM3 using multiple algorithms. Expressions of ACSM3 and AR were positively correlated in obese men and overweight women. ACSM3 expression was positively correlated with BMI in men and overweight women. Conclusion: ACSM3 expression is associated with obesity in MM patients and correlates with AR. Functional analysis linking the findings to the obesity paradox warrants further study.