Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy

Abstract Although immunotherapy has been predominant for advanced gastric cancer treatment, it still has limitations. Polyunsaturated fatty acids (PUFAs) are associated with inflammation while their roles in tumor immune microenvironment (TIME) are unclear. This study explores PUFAs’ impacts on gast...

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Main Authors: Dikan Wu, Fan Fan, Junxian He, Lian Wang, Caiyun Zhu, Yalin Ji, Haijun Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97644-6
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author Dikan Wu
Fan Fan
Junxian He
Lian Wang
Caiyun Zhu
Yalin Ji
Haijun Zhang
author_facet Dikan Wu
Fan Fan
Junxian He
Lian Wang
Caiyun Zhu
Yalin Ji
Haijun Zhang
author_sort Dikan Wu
collection DOAJ
description Abstract Although immunotherapy has been predominant for advanced gastric cancer treatment, it still has limitations. Polyunsaturated fatty acids (PUFAs) are associated with inflammation while their roles in tumor immune microenvironment (TIME) are unclear. This study explores PUFAs’ impacts on gastric cancer immunity and immunotherapy efficacy. Bioinformatics analysis was conducted to identify differential expressions of PUFAs metabolic genes and their immune correlations. Clinical data of advanced gastric cancer patients receiving immunotherapy at Zhongda Hospital (2020–2024), whose serum PUFAs were measured by mass spectrometry (MS), were collected and analyzed. Bioinformatics analysis revealed differential expression of half of PUFAs metabolic genes in gastric cancer. PUFAs metabolism towards Omega-3 (ω-3) tended to increase infiltration of active anti-tumor cells and up-regulate multiple immune checkpoints expressions, while metabolism towards Omega-6 (ω-6) led to opposite TIME outcomes. The clinical study demonstrated that lower serum ω-6/ω-3 ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, linoleic acid/alpha-linolenic acid (LA/ALA) ratio and higher EPA were associated with better six-month progression-free survival rate (6-month PFS) and one-year overall survival rate (1-year OS). This study deepens our understandings of TIME in gastric cancer. It clearly demonstrates that maintaining appropriate PUFAs ratios or values is promising in improving prognosis.
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spelling doaj-art-2b37a74fa73c4f4db1ca2663f16a371a2025-08-20T02:05:41ZengNature PortfolioScientific Reports2045-23222025-06-0115111210.1038/s41598-025-97644-6Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapyDikan Wu0Fan Fan1Junxian He2Lian Wang3Caiyun Zhu4Yalin Ji5Haijun Zhang6Department of Oncology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Oncology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Oncology, Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Oncology, Xuyi County People’s HospitalDepartment of Oncology, Xuyi County People’s HospitalDepartment of Oncology, Xuyi County People’s HospitalDepartment of Oncology, Zhongda Hospital, School of Medicine, Southeast UniversityAbstract Although immunotherapy has been predominant for advanced gastric cancer treatment, it still has limitations. Polyunsaturated fatty acids (PUFAs) are associated with inflammation while their roles in tumor immune microenvironment (TIME) are unclear. This study explores PUFAs’ impacts on gastric cancer immunity and immunotherapy efficacy. Bioinformatics analysis was conducted to identify differential expressions of PUFAs metabolic genes and their immune correlations. Clinical data of advanced gastric cancer patients receiving immunotherapy at Zhongda Hospital (2020–2024), whose serum PUFAs were measured by mass spectrometry (MS), were collected and analyzed. Bioinformatics analysis revealed differential expression of half of PUFAs metabolic genes in gastric cancer. PUFAs metabolism towards Omega-3 (ω-3) tended to increase infiltration of active anti-tumor cells and up-regulate multiple immune checkpoints expressions, while metabolism towards Omega-6 (ω-6) led to opposite TIME outcomes. The clinical study demonstrated that lower serum ω-6/ω-3 ratio, arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio, linoleic acid/alpha-linolenic acid (LA/ALA) ratio and higher EPA were associated with better six-month progression-free survival rate (6-month PFS) and one-year overall survival rate (1-year OS). This study deepens our understandings of TIME in gastric cancer. It clearly demonstrates that maintaining appropriate PUFAs ratios or values is promising in improving prognosis.https://doi.org/10.1038/s41598-025-97644-6Gastric cancerPUFAsTumor immune microenvironmentImmunotherapyBioinformatics analysisMass spectrometry
spellingShingle Dikan Wu
Fan Fan
Junxian He
Lian Wang
Caiyun Zhu
Yalin Ji
Haijun Zhang
Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
Scientific Reports
Gastric cancer
PUFAs
Tumor immune microenvironment
Immunotherapy
Bioinformatics analysis
Mass spectrometry
title Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
title_full Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
title_fullStr Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
title_full_unstemmed Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
title_short Effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
title_sort effects of polyunsaturated fatty acids on gastric cancer immunity and immunotherapy
topic Gastric cancer
PUFAs
Tumor immune microenvironment
Immunotherapy
Bioinformatics analysis
Mass spectrometry
url https://doi.org/10.1038/s41598-025-97644-6
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