Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular carcinoma (HCC) epithelial–mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.

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Background: The combination of anti-angiogenesis and immune checkpoint blockade has been proved to improve clinical outcomes of advanced HCC. We assessed the efficacy and safety of HAIC combined with apatinib and camrelizumab for BCLC stage C HCC.Methods: Consecutive treatment-naïve patients with BCLC stage C HCC were enrolled in this phase II trial (NCT04191889). Eligible patients were administrated with HAIC (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and fluorouracil 2500 mg/m 2 ; q3w; 6 cycles), combined with apatinib (250 mg qd) and camrelizumab (200 mg q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Following an optimal Simon 2-stage design, 26 eligible patients needed to be included in the first stage, of whom at least 11 patients had to achieve objective responses to warrant further investigation in the second stage.Results: From April 13th, 2020 to March 19th, 2021, 26 eligible patients were enrolled. As of April 30th, 2021, the median follow-up was 8.87 months and all patients had at least one post-baseline tumor assessment. The confirmed ORR was 61.54% (95% CI, 42.54%e77.57%) with 16 partial responses (PR) per RECIST v1.1, which met the threshold for expanding enrollment, while 76.92% (95% CI, 57.95%e 88.96%) with 2 (7.69%) complete responses (CR) and 18 (69.23%) PR per mRECIST. The disease control rate (DCR) was 92.31% (95% CI, 75.86%-97.87%) whether per RECIST v1.1 or mRECIST. The median time to response (mTTR) was 2.37 months (interquartile range (IQR), 1.39-2.76) per RECIST v1.1 or 1.67 months (IQR, 1.37-2.72) per mRECIST. The estimated 6-month progression-free survival (PFS) rate was 73.7% per RECIST v1.1, while the 12-month overall survival rate was 90.7%. Grade !3 adverse events (AEs) occurred in 69.23% of the patients, of which the most common were decreased neutrophils (38.46%), decreased lymphocytes (34.62%), and increased ALT and AST (26.92% for each). Conclusions:The triplet treatment of HAIC, apatinib and camrelizumab showed promising clinical benefits and acceptable safety for BCLC Stage C HCC.Clinical trial identification: NCT04191889.