Identification of novel antioxidant gene signature to predict the prognosis of patients with gastric cancer

Jianhua Wu; Xuan Wang; Nan Wang; Li Ma; Xin Xie; Hao Zhang; Huafeng Kang; Zhangjian Zhou

doi:10.1186/s12957-021-02328-w

Identification of novel antioxidant gene signature to predict the prognosis of patients with gastric cancer

World J Surg Oncol. 2021 Jul 20;19(1):219. doi: 10.1186/s12957-021-02328-w.

Authors

Jianhua Wu¹, Xuan Wang², Nan Wang¹, Li Ma¹, Xin Xie², Hao Zhang², Huafeng Kang³, Zhangjian Zhou⁴

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. kanghuafeng1973@126.com.
⁴ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. zhouzhangjian@xjtu.edu.cn.

Abstract

Background: Gastric cancer (GC) commonly relates to dismal prognosis and lacks efficient biomarkers. This study aimed to establish an antioxidant-related gene signature and a comprehensive nomogram to explore novel biomarkers and predict GC prognosis.

Methods: Clinical and expression data of GC patients were extracted from The Cancer Genome Atlas database. Univariate and multivariate Cox analyses were utilized to construct a score-based gene signature and survival analyses were conducted between high- and low-risk groups. Furthermore, we established a prognostic nomogram integrating clinical variables and antioxidant-related gene signature. Its predictive ability was validated by Harrell' concordance index and calibration curves and an independent internal cohort verified the consistency of the antioxidant gene signature-based nomogram.

Results: Four antioxidant-related genes (CHAC1, GGT5, GPX8, and PXDN) were significantly associated with overall survival of GC patients but only two genes, CHAC1 (HR = 0.803, P < 0.05) and GPX8 (HR = 1.358, P < 0.05), were confirmed as independent factors. A score-based signature was constructed and could act as an independent prognosis predictor (P < 0.05). Patients with lower scores showed significantly better prognosis (P < 0.05). Comprehensive nomogram combining the antioxidant-related gene signature and clinical parameters (age, gender, grade, and stage) was established and effectively predicted overall survival of GC patients [3-year survival AUC = 0.680, C index = 0.665 (95% CI 0.614-0.716)]. The independent internal validation cohort verified the reliability and good consistency of the model [3-year survival AUC = 0.703, C index = 0.706 (95% CI 0.612-0.800)].

Conclusions: Innovative antioxidant-related gene signature and nomogram performed well in assessing GC prognoses. This study enlightened further investigation of antioxidant system and provided novel tools for GC patient management.

Keywords: Antioxidants; Gastric cancer; Gene signature; Nomogram model; Prognosis.

MeSH terms

Antioxidants
Humans
Nomograms
Peroxidases
Prognosis
Reproducibility of Results
Stomach Neoplasms* / genetics

Substances

Antioxidants
GPX8 protein, human
Peroxidases