Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11% in the United States. As for other types of tumors, such as colorectal cancer, aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.

Aim: To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid (FA) import into cell.

Methods: A gene expression analysis of FASN, CD36, SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, ACSL1, and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection. The genes were considered significantly dysregulated between the groups when the p value was < 0.05 and the fold change (FC) was ≤ 0.5 and ≥ 2.

Results: We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue: SLC27A2 (FC = 5.66; P = 0.033), SLC27A3 (FC = 2.68; P = 0.040), SLC27A4 (FC = 3.13; P = 0.033), ACSL1 (FC = 4.10; P < 0.001), and ACSL3 (FC = 2.67; P = 0.012). We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors, including the anatomic location, the lymph node involvement, and the presence of metastasis. A significant difference in the expression of SLC27A3 (FC = 3.28; P = 0.040) was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.

Conclusion: Despite the low number of patients analyzed, these preliminary results seem to be promising. Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy. Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.