Title : ACSL4: A potential prognostic biomarker for patients with melanoma
Abstract:
Ferroptosis is characterized by the accumulation of lipid reactive oxygen species that have been oxidized by iron. There are many regulators of ferroptosis.One of these regulators is acyl-CoA synthetase long chain family member 4 (ACSL4).ACSL4 is a family of five enzymes that are expressed on the endoplasmic reticulum and the outer membranes of mitochondria and they function to catalyze the conversion of fatty acids into acyl-CoAs.ACSL4 was determined to increase cell sensitivity to ferroptosis, making this form of cell death more likely.Given this information,ACSL4 has now been identified as a target for therapeutic treatment approaches for diseases related to ferroptosis.Acyl-CoAs play a role in fatty acid metabolism,including fatty acid metabolic processes that result in cellular membrane modifications.Based on current available data,it seems that high levels of ACSL4 in cancers that typically highly express ACSL4 predicts a poorer prognosis. Similarly,low levels of ACSL4 in cancers that typically lowly express ACSL4 predicts a poorer prognosis.Thus,it is possible that reversing the level of ACSL4 expression to oppose the usual pattern of expression in a particular type of cancer may be an option for a therapeutic approach. Elucidating the role of ACSL4 expression in melanoma is important not only to improve the understanding of the role of ACSL4 in melanoma cells, but also to potentially guide future therapeutic options and prognostic counseling for patients. We investigated ACSL4 expression level (high or low) and the survival fraction and immune cell tumor infiltration in in patients with melanoma. The results collectively suggest that ACSL4 expression is positively correlated with the responses of patients to immune checkpoint inhibitors. ACSL4 expression is also positively correlated with tumor-infiltrating immune cells. The results of this study suggest that ACSL4 expression in melanoma cells improves survival likely through ferroptotic-mediated cell death, and is also more highly expressed in metastatic disease. Future research efforts should be directed toward elucidating the effect of ACSL4 expression on survival in melanoma patients with metastatic disease, differentiated by the type of metastasis occurring (lymphatic or hematogenous). Also, future studies may further investigate the role of ACSL4 expression in mediating immune cell infiltration into tumor cells, and the mechanisms by which this process facilitates tumor cell death. Once the role of ACSL4 in melanoma is more thoroughly understood and fully elucidated, its expression may be used as a prognostic indicator that can guide patient counseling and also may be used as a target for future therapies that aim to alter its
expression.
Audience Take Away Notes :
• Appreciate ACSL4 as a possible future marker for melanoma prognosis in patients
• Expand on this research by investigating the effect of ACSL4 expression based on type of metastatic spread
• Expand on this research by investigating possible roles for ACSL4 in promoting immune cell invasion
• Increase awareness of the body of literature regarding ACSL4 expression in cancers and how conflicting results exist about the effect of ACSL4 expression on prognosis in different types of cancer
