Distinct miRNA expression profiles in subcutaneous and visceral adipose tissue of gastrointestinal cancer patients and their modulation based on adiposity level assessed by CT-scan.

Abstract

MicroRNAs regulate adipose tissue function, but their depot-specific expression in cancer remains poorly understood. This study analyzed the expression of selected microRNAs in subcutaneous (SAT) and visceral adipose tissue (VAT) of gastrointestinal cancer patients versus controls to elucidate their roles in adipose tissue remodeling. We conducted a cross-sectional study including gastrointestinal cancer patients and controls undergoing surgery for malignant or benign conditions. SAT and VAT biopsies were collected intraoperatively for miRNA expression analysis by RT-qPCR. Adiposity was evaluated by CT-scan to quantify total adipose tissue and categorize participants according to median adiposity level. Gastrointestinal cancer patients vs. controls showed higher relative expression of miR-128 in both SAT and VAT (p = 0.006 and p = 0.040), miR-155 in VAT (p = 0.018), and lower miR-181a in VAT (p = 0.004). Within cancer group, miR-26a and miR-128 were lower in VAT vs SAT (p < 0.001), while miR-155 levels were higher in VAT vs SAT (p < 0.001). MiR-26a was higher in SAT regardless of adiposity level, while miR-128 and miR-144 showed depot- and adiposity-dependent variations, with downregulation of miR-128 in VAT from low-adiposity patients and lower miR-144 in SAT from high-adiposity. MiR-155 was elevated in VAT from low-adiposity patients, whereas miR-181a expression remained unchanged across depots and adiposity levels. This is the first study comparing both SAT and VAT microRNA from the same cancer patients, stratified by adiposity assessed via CT-scan, showing depot-specific miRNA regulation. Our findings indicate that VAT is prone to metabolic dysregulation, with miR-155 emerging as a potential indicator of visceral fat remodeling.