Association between Galectin-1 expression and metabolic parameters on ¹⁸F-FDG PET/CT in patients with surgically resected lung adenocarcinoma

Objectives: Galectin-1(Gal-1), a glycan-binding protein, is commonly overexpressed and considered as a novel molecular target for immunotherapy of lung cancer. Noninvasive imaging modality to estimate the status of Gal-1 and evaluate tumor response is helpful in clinical practice. ¹⁸F-FDG PET/CT has been proved to be useful in the diagnosis and monitor response of tumors. However, the relationship between Gal-1 expression and FDG metabolism has not been investigated yet. This study aimed to identify the correlation of Gal-1 expression with metabolic parameters on PET/CT and whether or not PET/CT could be used to predict the Gal-1 expression in resected lung adenocarcinoma patients. Furthermore, the prognostic significance of Gal-1 expression and metabolic parameters provided by PET/CT are investigated.

Methods: Ninety-six lung adenocarcinoma patients who underwent preoperative PET/CT were retrospectively analyzed in this study. Expression of Gal-1 and two key glycolysis-related enzymes, glucose transporter 1 (GLUT1) and hexokinase 2 (HK2), were examined by immunohistochemistry. Maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary tumor were measured in all PET/CT images. The relationship between metabolic parameters, clinicopathological factors and Gal-1 expression was analyzed using the Mann-Whitney U test and chi-square test, respectively. The association between SUV_max, Gal-1 and GLUT1 and HK2 were analyzed by Spearman rank correlation. Logistic regression analysis was used to identify predictors of Gal-1 expression. The optimal cutoff value of SUV_max was calculated using receiver operating characteristic curve (ROC). Progression-free survival (PFS) and overall survival (OS) were performed using Kaplan Meier curves, log-rank test and Cox proportional hazards model.

Results: Positive Gal-1 expression was found more frequently in patients with lymph node metastasis (P=0.000), advanced stage (P=0.000), moderately or poorly differentiated type (P=0.000). The tumor size was larger in the Gal-1-positive group than in the Gal-1-negative group (P=0.013). SUV_max, MTV and TLG were significantly higher in patients with Gal-1-positive group than in those Gal-1-negative group (P=0.000, P=0.000, P=0.000). SUV_max was the only independent predictor of Gal-1 expression. The optimal cutoff value of SUV_max that predicted Gal-1 expression was 5.1 in the ROC analysis [AUC 0.937(0.882-0.992)/P=0.000] with a sensitivity of 95.2% and specificity of 87.0%. There was a statistically significant positive correlation of Gal-1 with SUV_max, GLUT1 and HK2 (all P=0.000). There was also a strong positive correlation of SUV_max with GLUT1 and HK2 (P=0.000). Gal-1-positive patients showed significantly shorter PFS (P=0.000) and OS (P=0.001) than Gal-1-negative patients. In multivariate analysis of PFS, advanced stage (P=0.001) and positive Gal-1 expression (P=0.000) were significant independent prognostic factors. Multivariate analysis of OS revealed that advanced stage (P=0.000) and SUV_max (P=0.024) were significant independent prognostic factors.

Conclusions: ¹⁸F-FDG PET/CT could predict Gal-1 expression of lung adenocarcinoma patients as a noninvasive image tool. Gal-1 expression and SUV_max were significant predictor for PFS and OS, respectively.