A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma.

Zaisheng Ye,Shu Chen,He Huang,Yi Wang,Yi Zeng,Zhitao Lin,Qinying Liu,Qiuhong Zheng,Miao Zheng,Shenghong Wei,Luchuan Chen

doi:10.3389/fonc.2021.612952

Zaisheng Ye, Shu Chen + Show 9 more

Open Access

https://doi.org/10.3389/fonc.2021.612952

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Abstract

Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meaningful. An integrative analysis was performed with 407 samples from The Cancer Genome Atlas (TCGA) and 433 samples from Gene Expression Omnibus (GEO) to develop a metabolic prognostic signature associated with clinical and immune features in STAD using Cox regression analysis and least absolute shrinkage and selection operator (LASSO). The different proportions of immune cells and differentially expressed immune-related genes (DEIRGs) between high- and low-risk score groups based on the metabolic prognostic signature were evaluated to describe the association of cancer metabolism and immune response in STAD. A total of 883 metabolism-related genes in both TCGA and GEO databases were analyzed to obtain 184 differentially expressed metabolism-related genes (DEMRGs) between tumor and normal tissues. A 13-gene metabolic signature (GSTA2, POLD3, GLA, GGT5, DCK, CKMT2, ASAH1, OPLAH, ME1, ACYP1, NNMT, POLR1A, and RDH12) was constructed for prognostic prediction of STAD. Sixteen survival-related DEMRGs were significantly related to the overall survival of STAD and the immune landscape in the tumor microenvironment. Univariate and multiple Cox regression analyses and the nomogram proved that a metabolism-based prognostic risk score (MPRS) could be an independent risk factor. More importantly, the results were mutually verified using TCGA and GEO data. This study provided a metabolism-related gene signature for prognostic prediction of STAD and explored the association between metabolism and the immune microenvironment for future research, thereby furthering the understanding of the crosstalk between different molecular mechanisms in human STAD. Some prognosis-related metabolic pathways have been revealed, and the survival of STAD patients could be predicted by a risk model based on these pathways, which could serve as prognostic markers in clinical practice.

Highlights

Stomach adenocarcinoma (STAD) accounts for 95% of stomach tumors, which is associated with high mortality (1)
Analysis of DEMRGs between tumor and normal tissues in STAD was performed in the The Cancer Genome Atlas (TCGA) group
184 DEMRGs were identified as DEMRGs between tumor and normal tissues based on TCGA data (Figure 1 and Supplementary Table 3)

Summary

Introduction

Stomach adenocarcinoma (STAD) accounts for 95% of stomach tumors, which is associated with high mortality (1). The most effective treatment is radical surgery in the early stages combined with chemotherapy, postoperative radiotherapy, and lymphadenectomy, but 65% of patients with STAD presented at an advanced stage, and nearly 85% of patients with STAD display lymph node metastasis at the time of diagnosis (2). Despite the decreasing incidence worldwide, the 5-year survival rate of patients with resectable STAD ranges from 10% to 30% (3). STAD can be treated with radical surgery and adjuvant therapy, more than 40% of patients continue to experience recurrence or tumor metastasis (4). The association between microarray-based gene expression profiling and the corresponding phenotypic changes in STAD has allowed accurate early diagnosis or evaluation of prognosis (5). The development of novel biomarkers in STAD would aid early diagnosis, guide surgical and adjuvant therapy decision making, and provide potential therapeutic targets

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