Abstract

BackgroundFerroptosis is a novel form of regulated cell death that plays a critical role in tumorigenesis. The purpose of this study was to establish a ferroptosis-associated gene (FRG) signature and assess its clinical outcome in gastric cancer (GC).MethodsDifferentially expressed FRGs were identified using gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed to construct a prognostic signature. The model was validated using an independent GEO dataset, and a genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features was established.ResultsAn 8-FRG signature was constructed to calculate the risk score and classify GC patients into two risk groups (high- and low-risk) according to the median value of the risk score. The signature showed a robust predictive capacity in the stratification analysis. A high-risk score was associated with advanced clinicopathological features and an unfavorable prognosis. The predictive accuracy of the signature was confirmed using an independent GSE84437 dataset. Patients in the two groups showed different enrichment of immune cells and immune-related pathways. Finally, we established a genomic-clinicopathologic nomogram (based on risk score, age, and tumor stage) to predict the overall survival (OS) of GC patients.ConclusionsThe novel FRG signature may be a reliable tool for assisting clinicians in predicting the OS of GC patients and may facilitate personalized treatment.

Highlights

  • Gastric cancer (GC) is a major malignant tumor with an incidence of 5.7% and a mortality rate of 8.2% based on global cancer statistics in 2018

  • A high-risk score was associated with advanced clinicopathological features and an unfavorable prognosis

  • The novel ferroptosis-related genes (FRGs) signature may be a reliable tool for assisting clinicians in predicting the overall survival (OS) of GC patients and may facilitate personalized treatment

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Summary

Introduction

Gastric cancer (GC) is a major malignant tumor with an incidence of 5.7% and a mortality rate of 8.2% based on global cancer statistics in 2018. Despite continuous improvements in surgery, advanced imaging techniques, and the development of new drug, an inefficient early diagnosis rate may result in a limited five-year survival in cases of GC [1,2]. Various studies have revealed that ferroptosis can inhibit tumor growth and development, and ferroptosis induction inhibits the progression of chemotherapy-resistant tumors [5,6]. Multiple genes, such as P53 [7], RSL3 [8], FSP1 [9], and SLC7A11 [10], modulate sensitivity to or are markers of ferroptosis. The purpose of this study was to establish a ferroptosis-associated gene (FRG) signature and assess its clinical outcome in gastric cancer (GC)

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