Relationships among polyunsaturated fatty acid profiles, immune landscapes, and immunotherapy prognoses in gastric cancer.

Abstract

e14560 Background: Advanced gastric cancer patients undergoing first-line immunotherapy combined with chemotherapy often experience suboptimal outcomes. This is mainly due to our incomplete understanding of the tumor immune microenvironment (TIME). Polyunsaturated fatty acids (PUFAs) are closely associated with inflammation, yet their roles within the TIME are not well understood. This research focuses on exploring the relationship between serum PUFAs, measured by mass spectrometry (MS), and the effectiveness of immunotherapy in gastric cancer. Methods: Clinical data of patients who received immunotherapy at Zhongda Hospital from 2022-2023 were collected. Serum PUFAs were measured using the accurate quantitative tool mass spectrometry (MS), and then analyzed to determine their correlations with treatment efficacy. Results: The clinical study demonstrated that the serum ω-6/ω-3 ratio was an independent risk factor for disease control rate (DCR), and serum eicosapentaenoic acid (EPA) was an independent protective factor for DCR. The serum arachidonic acid (AA)/EPA ratio was an independent risk factor for objective response rate (ORR). In the long-term efficacy analysis, the serum linoleic acid (LA)/ alpha-linolenic acid (ALA) and serum AA/EPA ratios were independent risk factors for disease progression, and serum EPA was an independent protective factor for disease progression. The serum AA/EPA ratio was an independent risk factor for one-year survival. In terms of predictive values, the serum AA/EPA ratio (AUC = 0.82, P = 0.002) and serum EPA (AUC = 0.84, P < 0.001) were strong predictors of the six-month progression-free survival rate (6-month PFS). The AA/EPA ratio (AUC = 0.80, P = 0.008) was also a significant predictor of the one-year overall survival rate (1-year OS). Conclusions: This study has discovered the relationships between serum PUFAs profiles and immunotherapy prognoses in gastric cancer. We presume that maintaining appropriate PUFAs ratios or levels might enhance the effectiveness of immunotherapy.