Galectin-1 Modulates Hepatocellular Carcinoma Response to Thermal Ablation Through Regulating Glycolysis

Abstract

I.Background & AimsThermal ablation is the standard of care treatment modality with curative intent for early-stage hepatocellular carcinoma (HCC), but its efficacy remains moderately limited-- with up to 40% of HCC patients experiencing local recurrence post-treatment. This study aimed to evaluate the prognostic value of galectin-1 (Gal-1) in predicting thermal-ablation responsiveness. We then evaluated the therapeutic potential of targeting Gal-1 in inhibition of glycolysis and subsequently enhancing thermal-ablation efficacy. MethodsLiquid-Chromatography Mass-Spectrometry (LC-MS) was employed to analyze proteomic profiles of retrospectively collected pre-ablation FFPE samples of known thermal-ablation responders and nonresponders. An in-vitro thermal peri-ablation model was established using a heated water bath. Gal-1 inhibition via OTX008 or knockdown was utilized to investigate hyperthermic sensitivity. Hyperthermia-resistant SNU449 cells were used to establish an orthotopic murine model to evaluate the combination therapy of OTX008 and thermal ablation. Harvested tumors were analyzed by LC-MS to determine their metabolic profiles. ResultsThis study revealed that responders had significantly longer tumor progression-free survival compared to nonresponders (57.0{+/-}1.6 (median not reached) versus 8.3{+/-}0.5 months (median: 13.6 months), p View larger version (27K): org.highwire.dtl.DTLVardef@18788ccorg.highwire.dtl.DTLVardef@1261839org.highwire.dtl.DTLVardef@5d57org.highwire.dtl.DTLVardef@1f00b2a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIProfiling pre-ablation HCC biopsies reveals Galectin-1 as a key prognostic biomarker for response prediction in thermal ablation C_LIO_LITargeting Galectin-1 with a selective inhibitor (OTX008) enhances the efficacy of thermal ablation in HCC C_LIO_LIGalectin-1 modulates thermal-ablation response via regulating glycolysis in HCC C_LI