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.
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Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by grant number 04-2021-3110 from the SNUH Research Fund.
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JSK and DWK conceived and designed the analysis. JSK, SK, and JK collected the data. JSK, SK, JK, and DWK contributed data or analysis tools. JSK, SK, JK, and DWK performed the analysis. JSK, SK, JK, MK, BK, TMK, BL, and DWK wrote the paper. All the authors read and approved the final manuscript.
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Conflict of interest
Dr. D-W Kim’s Institution (Seoul National University Hospital) received grants from Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, BMS, Bridge BioTherapeutics, Chong Keun Dang, Daiichi-Sankyo, GSK, Hanmi, InnoN, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan. In addition, Dr. D-W Kim received travel support for advisory board meeting attendance from Amgen and Daiichi-Sankyo. All these COIs are outside of the submitted work. Dr. B Lindmark is an employee of Galecto, Inc. Dr. TM Kim’s institution received clinical trial budgets from AstraZeneca/MedImmune, Bayer, Boehringer-Ingelheim, Boryung, Genmab, Hanmi, Janssen, Merck Serono, Merck Sharp & Dohme Corp, Novartis, REGENERON, Roche/Genentech, Sanofi, and Takeda. Dr. TM Kim received advisory or consulting fees from AstraZeneca, Hanmi, Janssen, Novartis, Roche/Genentech, and Takeda. In addition, Dr. TM Kim received research grant from AstraZeneca-KHIDI outside this work. Dr. M Kim received advisory or consulting fees from Merck Sharp & Dohme Corp, Ipsen, Bristol-Myers Squibb/Ono Pharmaceutical, Eisai, and Yuhan. No conflicts of interest are disclosed by the other authors.
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The study was conducted in accordance with the Principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of the SNUH (IRB No. H-2006-146-1134).
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Kim, J.S., Kim, S., Koh, J. et al. 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. J Cancer Res Clin Oncol 149, 2355–2365 (2023). https://doi.org/10.1007/s00432-022-04275-9
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DOI: https://doi.org/10.1007/s00432-022-04275-9