Serum NGAL and G-CSFR as Predictive and Prognostic Biomarkers for Trastuzumab-Based Therapy in HER2-Positive Gastric
Jingwen Ying1, Zui Wang1, Jing Wang2
1Department of Pharmacy, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang, 315000, People's Republic of China.
Objective:
To evaluate serum neutrophil gelatinase-associated lipocalin (NGAL) and granulocyte colony-stimulating factor receptor (G-CSFR) in predicting efficacy and prognosis of trastuzumab-based targeted therapy in HER2-positive gastric cancer patients.
Methods:
This retrospective study enrolled 150 patients with HER2-positive gastric cancer who were admitted to our hospital between January 2023 and January 2025. All patients received trastuzumab-based combination chemotherapy (XELOX or SOX regimen) and were categorized into responders and non-responders according to the RECIST 1.1 criteria. Baseline patient data and clinicopathological parameters related to gastric cancer were retrospectively collected. Serum levels of NGAL and G-CSFR were measured at three time points: before treatment (T0), after 2 cycles of therapy (T1), and after 4 cycles of therapy (T2). Differences in the dynamic changes of these biomarkers between groups were compared. Multivariate logistic regression analysis was performed to identify independent prognostic factors. ROC curves were constructed to evaluate the predictive performance of NGAL, G-CSFR, and their combined use for assessing the efficacy of trastuzumab-based targeted therapy in HER2-positive gastric cancer patients. Kaplan‑Meier analysis was used to assess the relationship between different NGAL and G‑CSFR levels and progression‑free survival (PFS).
Results:
The proportions of TNM stage IV, HER2 FISH-positive status, and poorly differentiated pathological types were significantly higher in the non-responder group than in the responder group (P < 0.05). At T0, T1, and T2, serum NGAL levels were significantly higher in the non-responder group than in the responder group, and G-CSFR levels were significantly lower (P < 0.05). In both groups, NGAL levels progressively decreased over the treatment course, while G-CSFR levels progressively increased (P < 0.05). Multivariate logistic regression analysis identified poor differentiation and higher T0 NGAL levels as independent risk factors for non-response to trastuzumab-based targeted therapy in HER2-positive gastric cancer patients, while higher T0 G-CSFR levels served as an independent protective factor (P < 0.05). ROC curve analysis demonstrated that the combination of NGAL and G-CSFR at T0 yielded an AUC of 0.813 for predicting treatment response, which was significantly superior to that of either single marker (NGAL: 0.656; G-CSFR: 0.731). The combined assay achieved a sensitivity of 0.766 and a specificity of 0.751. Kaplan-Meier analysis showed that the high NGAL group had a median PFS of 6.0 (5.0, 9.0) months, significantly shorter than the low NGAL group with 7.0 (7.0, 11.0) months (Log-rank χ2 = 6.511, P = 0.011); the low G-CSFR group had a median PFS of 6.0 (5.0, 8.0) months, significantly shorter than the high G-CSFR group with 8.0 (8.0, 11.0) months (Log-rank χ2 = 15.968, P < 0.001).
Conclusion:
Baseline serum levels of NGAL and G-CSFR prior to treatment are closely associated with the efficacy of trastuzumab-based targeted therapy in patients with HER2-positive gastric cancer. The combination of these two biomarkers significantly improves the predictive performance for treatment response. Moreover, baseline NGAL and G-CSFR levels can effectively estimate patient PFS, suggesting their potential utility as non-invasive clinical biomarkers for predicting treatment efficacy and prognosis in HER2-positive gastric cancer patients receiving trastuzumab-based therapy.