Tissue galectin-3 as a potential prognostic biomarker in type 2 diabetes patients with hepatocellular carcinoma: in vitro and in silico approaches

Abstract Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia, generating circulating glycated albumin (GA). The development and progression of liver cancer, and more specifically hepatocellular carcinoma (HCC), are increased in patients with T2D. To facilitate early diagnosis and appropriate therapeutic strategies, we sought to identify novel HCC biomarkers in these patients by investigating the biological impact of GA on HepG2 and metastatic HuH7 HCC cell lines. After treatment with various concentrations (25–200 µg/mL) of methylglyoxal-derived GA, cell viability, migration, and invasion were assessed, respectively, by CellTiter-Glo ® , scratch assay, and Matrigel™-coated Transwell™ inserts. The expression of signaling and oncology-related proteins was monitored using Western blot and protein array analyses. GA significantly and dose-dependently modulated cell viability, wound healing, and oncogenic p-ERK according to a bell-shaped curve, compared to untreated cells, the control. At 100 µg/mL, GA significantly stimulated cell invasion and augmented ribosomal protein S6 phosphorylation, EpCAM, and galectin-3 expression in metastatic HuH7 cells, mainly to a lesser extent in HepG2 cells. TCGA database analysis revealed, unlike EpCAM, a positive correlation between the high expression levels of genes encoding pS6 kinase and galectin-3, and liver cancer patients’ high BMI, advanced stages of HCC, metastatic status, and poor overall survival. By immunohistochemical staining, only galectin-3 was detected significantly in HCC tissues from T2D Saudi patients compared to their non-diabetic counterparts. A larger cohort is needed to evaluate galectin-3 expression as a potential biomarker and its prognostic values in T2D patients with HCC.