Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer

Abstract

Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

Keywords: ELISA; NSCLC; galectins; metastasis; non-small cell lung cancer; overall survival; prognosis; treatment.

Figure 1

Comparison of galectin-1, -3, and -9 levels by lung cancer stage (I-IV). Multiple comparisons were performed using one-way ANOVA. Gal = galectin; NSCLC = non-small cell lung cancer.

Figure 2

Comparison of galectin-1, -3, and -9 levels by lung cancer histology (adenocarcinoma and squamous cell carcinoma). Two group comparisons were performed by two-tailed t-test. ** p = 0.0019. Gal = galectin.

Figure 3

Comparison of galectin-1, -3, and -9 levels by previous lung cancer treatment type. All individual treatment agents and types of surgery received by patients are available in the Supplemental Data File S1. P-values, means, and standard deviations are shown in Table 2. Two group comparisons for radiation, surgery, chemotherapy, targeted therapy, and immunotherapy were made by two-tailed t-test. * p = 0.0375. Gal = galectin.

Figure 4

Comparison of galectin-1, -3, and -9 levels by those with metastatic disease at time of sample procurement. Two group comparisons were made by two-tailed t-test. * p = 0.0344. Gal = galectin.

Figure 5

Survival probability in all graphs represents survival without development of metastatic disease in patients with stage III disease or lower. If metastasis occurred, it was recorded from date of radiologic progression with physician documentation of metastases verified. Patients with stage IV disease at lung cancer tissue procurement were excluded from this analysis. In (A), patients were retrospectively followed by examining the time to developing metastasis based upon serum galectin-1 level stratified as low, normal, or high. In (B), patients with low or high galectin-1 levels were evaluated and combined into one group, called abnormal, and the time to developing metastasis was examined. (C,D) represent levels of galectin-3 and -9, respectively, while examining time to developing metastasis by serum galectin levels. Log Rank analysis was utilized for all graphs.

Figure 6

In (A), patients were stratified by serum galectin-1 levels, including low, normal, and high, and retrospectively followed until death or end of study duration. (B) combines patients with high or low galectin-1 levels into a category called abnormal, and patients with normal or abnormal galectin-1 level were followed till death or end of study duration. In (C,D), patients with normal and high galectin-3 and -9 levels, respectively, were followed until death or end of study duration. Log Rank analysis was utilized for all graphs.

Figure 7

(A) shows patients with adenocarcinoma grouped by normal and abnormal serum galectin-1 levels, which included those with high and low levels, followed from time of lung cancer tissue collection until death or end of study duration. In (B), patients with squamous cell carcinoma were stratified by serum galectin-1 levels, as described above, and followed until death or end of study duration. Log Rank analysis was utilized for all graphs.

Figure 8

(A) displays patients with surgically unresectable lung cancer grouped by normal and abnormal serum galectin-1 levels, which included those with high and low levels, followed from time of lung cancer tissue collection until death or end of study duration. In (B), patients with resectable lung cancer were stratified by serum galectin-1 levels, as described above, and followed until death or end of study duration. Log Rank analysis was utilized for all graphs.