Predictive role of galectin-3 for immune checkpoint blockades (ICBs) in advanced or metastatic non-small cell lung cancer: a potential new marker for ICB resistance

Abstract

Purpose: We aimed to assess the predictive value of galectin-3 (Gal-3) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint blockades (ICBs) therapy using both enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). Methods: This retrospective study was conducted at Seoul National University Hospital. Patients with EGFR/ALK-wild-type advanced or metastatic NSCLC who received ICBs between December 2013 and December 2019 were enrolled. Patients with archived blood samples collected prior to ICB treatment were assigned to the ELISA cohort. In addition, those with tissue samples from sites of recurrence or metastasis were assigned to an IHC cohort. Then, we analyzed Gal-3 expression in both cohorts. Results: Fifty-six patients in the ELISA cohort were grouped into low (N = 36) and high (N = 20) groups, using the mean Gal-3 ELISA level (13.24 pg/ml) as a cutoff. The high group demonstrated trends toward reduced progression-free survival (PFS) (0.9 vs. 3.7 months, p = 0.196) and significantly shorter overall survival (OS) (1.6 vs. 12.3 months, p = 0.018) than the low group. We categorized 94 patients in the IHC cohort into negative (N = 31) and positive (N = 63) groups based on Gal-3 IHC positivity. However, the median PFS (4.6 vs. 4.6 months for the negative vs. positive IHC group, respectively, p = 0.345) and OS (16.4 vs. 9.0 months, p = 0.137) were not significantly different. Conclusion: High blood Gal-3 levels may predict inferior survival in patients with advanced or metastatic NSCLC treated with ICBs.