463 Lipid metabolism reprogramming in eyelid sebaceous gland carcinoma

Abstract

Background Eyelid sebaceous gland carcinoma (SGC) is an aggressive malignancy.The status of lipid metabolism in SGC is not known. This study investigates Stearoyl-CoA desaturase (SCD1) and CD36 in eyelid SGC. SCD1 is the key rate-limiting enzyme of lipid metabolism and desaturates the saturated fatty acids (SFAs) to generate monounsaturated fatty acids (MUFAs). CD36 is a high-affinity receptor for long-chain fatty acids (FA) which facilitates FA uptake into the cell. CD36 functions as both a signal transducer and a fatty acid transporter. Both are upregulated in various cancers. Design This study evaluated 31 cases of histopathologically confirmed eyelid SGC and 10 normal controls (skin).Comprehensive qPCR gene expression profiles of SCD1 and CD36 and western blotting of SCD1 was done in all cases and controls. Patients were followed up for 25.71 ± 17.68 months. Statistical analysis was applied to determine the clinical significance of SCD-1 and CD-36. Results The mean age was 58.74 ±12.01 years, with a slight male predominance (55%). Tumors >2 cm were present in 25.8%, pagetoid spread in 45.1% and well differentiation was observed in 64.5% of the cases. There were 29% cases in AJCC T3/T4 stage. Four cases of recurrences, 2 with lymph nodes metastasis, one case each with distant metastasis and death. SCD1 and CD36 mRNA overexpression was observed in 67.7% and 61.2% patients respectively, 69.5% with age >50 years showed a high mRNA expression of SCD1 and 65.2% had high CD36. Females showed high SCD1 (85.7%) and CD36 (78.5%) expression and 57.1% of cases with pagetoid spread overexpressed both SCD-1 and CD-36. 62.5% of cases in T3/T4 stages showed high SCD-1 and 55.6% had high CD36 expression. Overexpression of SCD1 and CD36 was observed in 70% and 60% poorly differentiated tumors respectively. The single patient who died and 75% recurrent cases had high SCD1.CD36 overexpressed in all 4 recurrent cases and the patient who died. The mRNA expression of SCD1 correlated with mRNA expression of CD36 in 67.7% (21/31) cases. The protein expression of SCD1 by western blot correlated with the mRNA expression of SCD1. Conclusions In this first preliminary study on lipid metabolism in eyelid SGC patients, we observed upregulation of both SCD1 and CD36 in patients with poor prognostic features. A longer follow-up is warranted to confirm their roles as potential markers for identifying high-risk patients. SCD1 and CD36 could serve as molecular targets for therapeutic intervention in drug-resistant cases.