Galectin-9 in non-small cell lung cancer

Lung Cancer. 2019 Oct:136:80-85. doi: 10.1016/j.lungcan.2019.08.014. Epub 2019 Aug 16.

Abstract

Objectives: Lung cancer has the highest incidence and fatality among all cancers. Our research analyzed the expression of galectin-9 on non-small cell lung cancer (NSCLC) tumor cells and tumor infiltrating lymphocytes (TILs).

Materials and methods: We analyzed the expression level of galectin-9 protein in 136 NSCLC primary tumor samples by immunohistochemistry (IHC).

Results: We tested 136 surgical resected primary NSCLC tumor tissues for galectin-9 from Medical University of Gdansk, Poland. We found that on tumor cells, galectin-9 level only had correlation with T cell immunoglobulin and mucin-domain containing-3 (TIM-3) level (Correlation Coefficient = 0.360, p < 0.001). On TILs, galectin-9 level had broad connections with other checkpoints including programmed cell death protein-1 (PD-1) (Correlation Coefficient = 0.332, p < 0.001), programmed cell death-ligand 1 (PD-L1) (Correlation Coefficient = 0.247, p = 0.004) and TIM-3 (Correlation Coefficient = 0.350, p < 0.001). Interestingly, galectin-9 level on TILs also had positive relation with PD-L1 level on tumor cells (Correlation Coefficient = 0.278, p = 0.001), galectin-9 level on tumor cells (Correlation Coefficient = 0.181, p = 0.035) and TIL percentage (Correlation Coefficient = 0.236, p = 0.006). High level of galectin-9 on TILs indicated shorter RFS (recurrence-free survival) (RFS 1.82 years, 95% CI 0.795-2.845 vs. 0.67 years, 95% CI 0.086-1.254, P = 0.033). Patients with galectin-9 positive tumor cells display longer overall survival (OS) (1.76 years, 95% CI 0.222-3.298 vs. 3.10 years, 95% CI 2.662-3.538, P = 0.039) CONCLUSIONS: We found galectin-9 expression on both NSCLC tumor cells and TILs. Galectin-9 expression was found in all NSCLC pathological type. Galectin-9 level on TILs had correlation with TIM-3, PD-1 and PD-L1 level. On tumor cells, galectin-9 level had correlation with TIM-3 level. Patients with low galectin-9 level on tumor cells or high galectin-9 level on TILs were more likely to have poor prognosis.

Keywords: Galectin-9; NSCLC; PD-1; PD-L1; TILs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Female
  • Galectins / genetics
  • Galectins / metabolism*
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Galectins
  • LGALS9 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor