Fatty acid β-oxidation-associated prognostic model in gastric cancer and functional validation of IL-6 as a potential therapeutic target

Sep 23, 2026

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A prognostic framework links fatty acid β-oxidation (FAO) to gastric cancer progression, addressing unclear underlying mechanisms. FAO-associated genes were screened from GEO and TCGA transcriptomic datasets to derive a 160-gene signature and a risk scoring model stratifying patients into low- and high-risk groups. Immune phenotypes, drug sensitivities, and hub genes, including IL-6, were evaluated. Functional validation used immunoblotting and immunohistochemistry on gastric cancer cell lines and tissue samples, showing IL-6 as a core gene with consistent expression differences across cellular and tissue levels.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Introduction

Methods

Patients and histological samples

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Fatty acid β-oxidation-associated prognostic model in gastric cancer and functional validation of IL-6 asa potential therapeutic target Chao Qu1,2,8, XuetaoYuan2,8, Shuting Yang2, Yifan Qiao3, Renjianzhi Zhang4, Yunhua Wu5, Mengke Zhu6, Jiayin Du2, Gan Li2, Rui Zhang7, Xuejun Sun2􀀍 & Xuqi Li2􀀍 Gastric cancer (GC) poses a significant health threat, and alterations in Fatty acid β-oxidation (FAO) may influence its progression. However, the precise mechanisms underlying this association remain unclear. FAO-related genes were analyzed using transcriptomic datasets from databases of GEO and TCGA. Totally 160 FAO-associated genes were identified, and a risk scoring model was subsequently established to stratify patients into groups of low-and high-risk. Immune characteristics, drug sensitivities, and hub genes, including IL-6, were assessed. Subsequently, immunoblotting and immunohistochemistry were performed on GC cell lines and tissue samples to evaluate IL-6 expression. Analysis of theTCGA and GEO databases revealed a FAO-related gene signature comprising ACADS, ACO2, CPT2, SLC22A5, AOC3, CD36, CIDEA, G0S2, GABARAPL1, and SERINC1. We also examined gene mutations and constructed a prognostic risk scoring model with validation achieved through a nomogram to predict gastric cancer risk. Immune infiltration analysis and drug sensitivity testing (e.g. AG-014699, Axitinib, BX-795, and Cisplatin) were also conducted. IL-6 emerged as a core gene with significant expression difference across cellular and tissue levels. FAO plays a critical role in the prognosis of GC, and IL-6 may serve as a key biomarker for diagnosis and therapeutic strategies. Keywords Fatty acid β-oxidation, Gastric cancer, IL-6, Prognosis model Abbreviations FAO Fatty acid β-oxidation GC Gastric cancer EMT Elial-mesenchymal-transition TMB Tumor mutation burden IL-6 Interleukin-6 OS Overall survival DEG Differentially-expressed gene PFS Progression-free survival AUC Area under the curve GSVA Gene set variation analysis PCA Principal component analysis Gastric cancer (GC) remains a major global health challenge, ranking among the foremost contributors to cancer-associated mortality worldwide1,2. Currently, management of GC mainly relies on surgical resection 1Department of Abdominal Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 2Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 3Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 4Department of Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 5The Second Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China. 6Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 7Department of Critical Care Medicine, College of Medicine, Shaanxi Provincial Cancer Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China. 8Chao Qu and Xuetao Yuan have contributed equally to this work. 􀀍 email: [sunxy@mail.xjtu.edu.cn](sunxy@mail.xjtu.edu.cn); [lixuqi@163.com](lixuqi@163.com) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) together with perioperative combined chemotherapy and molecular targeted therapy, which, however, brings limited clinical benefits for patients. Thus further improvement in studies on treatment of GC is needed3–7. Fatty acid β-oxidation (FAO) constitutes the central process in cellular lipid metabolism, in which cells gradually break down long-chain fatty acids with energy released, and was known as a key biochemical process that regulates the abundance of ATP and NADPH8,9. Accumulating investigations have shown the pathogenic invo

FAQs

How were FAO-related genes and the prognostic model constructed?

FAO-associated genes were analyzed using transcriptomic datasets from GEO and TCGA, then a risk scoring model was established to stratify patients into low- and high-risk groups with validation via a nomogram.

What role does IL-6 play in the study’s findings?

IL-6 emerged as a core hub gene with significant expression differences across cellular and tissue levels. Experimental assays (immunoblotting and immunohistochemistry) were used to evaluate IL-6 expression in gastric cancer models.

Which additional analyses were performed beyond prognosis scoring?

The study assessed immune characteristics, immune infiltration, and drug sensitivities, and it examined gene mutations to support the FAO-related prognostic signature.

Sep 23, 2026

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