Dataset Information

Identification of a metabolic-related gene signature predicting the overall survival for patients with stomach adenocarcinoma.

ABSTRACT:

Background

The reprogramming of energy metabolism and consistently altered metabolic genes are new features of cancer, and their prognostic roles remain to be further studied in stomach adenocarcinoma (STAD).

Methods

Messenger RNA (mRNA) expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the GSE84437 databases from the Gene Expression Omnibus (GEO) database. A univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression model established a novel metabolic signature based on TCGA. The area under the receiver operating characteristic (ROC) curve (AUROC) and a nomogram were calculated to assess the predictive accuracy.

Results

A novel metabolic-related signature (including acylphosphatase 1, RNA polymerase I subunit A, retinol dehydrogenase 12, 5-oxoprolinase, ATP-hydrolyzing, malic enzyme 1, nicotinamide N-methyltransferase, gamma-glutamyl transferase 5, deoxycytidine kinase, galactosidase alpha, DNA polymerase delta 3, glutathione S-transferase alpha 2, N-acyl sphingosine amidohydrolase 1, and N-acyl sphingosine amidohydrolase 1) was identified. In both TCGA and GSE84437, patients in the high-risk group showed significantly poorersurvival than the patients in the low-risk group. A good predictive value was shown by the AUROC and nomogram. Furthermore, gene set enrichment analyses (GSEAs) revealed several significantly enriched pathways, which may help in explaining the underlying mechanisms.

Conclusions

A novel robust metabolic-related signature for STAD prognosis prediction was conducted. The signature may reflect the dysregulated metabolic microenvironment and can provided potential biomarkers for metabolic therapy in STAD.

SUBMITTER: Nie Y

PROVIDER: S-EPMC7877239 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Identification of a metabolic-related gene signature predicting the overall survival for patients with stomach adenocarcinoma.

Nie Yuan Y Liu Linxiang L Liu Qi Q Zhu Xuan X

PeerJ 20210208

<h4>Background</h4>The reprogramming of energy metabolism and consistently altered metabolic genes are new features of cancer, and their prognostic roles remain to be further studied in stomach adenocarcinoma (STAD).<h4>Methods</h4>Messenger RNA (mRNA) expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the GSE84437 databases from the Gene Expression Omnibus (GEO) database. A univariate Cox regression analysis and the least absolute shrinkage ...[more]

PMID: 33614297

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Project description:BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) is one of the main subtypes of lung cancer. Hundreds of metabolic genes are altered consistently in LUAD; however, their prognostic role remains to be explored. This study aimed to establish a molecular signature that can predict the prognosis in patients with LUAD based on metabolic gene expression.MethodsThe transcriptome expression profiles and corresponding clinical information of LUAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) between LUAD and paired non-tumor samples were identified by the Wilcoxon rank sum test. Univariate Cox regression analysis and the lasso Cox regression model were used to construct the best-prognosis molecular signature. A nomogram was established comprising the prognostic model for predicting overall survival. To validate the prognostic ability of the molecular signature and the nomogram, the Kaplan-Meier survival analysis, Cox proportional hazards model, and receiver operating characteristic analysis were used.ResultsThe six-gene molecular signature (PFKP, PKM, TPI1, LDHA, PTGES, and TYMS) from the DEGs was constructed to predict the prognosis. The molecular signature demonstrated a robust independent prognostic ability in the training and validation sets. The nomogram including the prognostic model had a greater predictive accuracy than previous systems. Furthermore, a gene set enrichment analysis revealed several significantly enriched metabolic pathways, which suggests a correlation of the molecular signature with metabolic systems and may help explain the underlying mechanisms.ConclusionsOur study identified a novel six-gene metabolic signature for LUAD prognosis prediction. The molecular signature could reflect the dysregulated metabolic microenvironment, provide potential biomarkers for predicting prognosis, and indicate potential novel metabolic molecular-targeted therapies.

Project description:BackgroundStomach adenocarcinoma (STAD), caused by mutations in stomach cells, is characterized by poor overall survival. Chemotherapy is commonly administered for stomach cancer patients following surgical resection. An imbalance in tumor metabolic pathways is connected to tumor genesis and growth. It has been discovered that glutamine (Gln) metabolism plays a crucial role in cancer. Metabolic reprogramming is associated with clinical prognosis in various cancers. However, the role of glutamine metabolism genes (GlnMgs) in the fight against STAD remains poorly understood.MethodsGlnMgs were determined in STAD samples from the TCGA and GEO datasets. The TCGA and GEO databases provide information on stemness indices (mRNAsi), gene mutations, copy number variations (CNV), tumor mutation burden (TMB), and clinical characteristics. Lasso regression was performed to build the prediction model. The relationship between gene expression and Gln metabolism was investigated using co-expression analysis.ResultsGlnMgs, found to be overexpressed in the high-risk group even in the absence of any symptomatology, demonstrated strong predictive potential for STAD outcomes. GSEA highlighted immunological and tumor-related pathways in the high-risk group. Immune function and m6a gene expression differed significantly between the low- and high-risk groups. AFP, CST6, CGB5, and ELANE may be linked to the oncology process in STAD patients. The prognostic model, CNVs, single nucleotide polymorphism (SNP), and medication sensitivity all revealed a strong link to the gene.ConclusionGlnMgs are connected to the genesis and development of STAD. These corresponding prognostic models aid in predicting the prognosis of STAD GlnMgs and immune cell infiltration in the tumor microenvironment (TME) may be possible therapeutic targets in STAD. Furthermore, the glutamine metabolism gene signature presents a credible alternative for predicting STAD outcomes, suggesting that these GlnMgs could open a new field of study for STAD-focused therapy Additional trials are needed to validate the results of the current study.

Project description:BackgroundIt has been widely reported that epithelial-mesenchymal transition (EMT) is associated with malignant progression in gastric cancer (GC). Integration of the molecules related to EMT for predicting overall survival (OS) is meaningful for understanding the role of EMT in GC. Here, we aimed to establish an EMT-related gene signature in GC.MethodsTranscriptional profiles and clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA). We constructed EMT-related gene signature for predicting OS by using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier analysis were performed to assess its predictive value. A nomogram combining the prognostic signature with clinical characteristics for OS prediction was established. And its predictive power was estimated by concordance index (C-index), time-dependent ROC curve, calibration curve and decision curve analysis (DCA). GSE62254 dataset from Gene Expression Omnibus (GEO) was used for external validation. Quantitative real-time PCR (qRT-PCR) was used to detected the mRNA expression of the five EMT-related genes in human normal gastric mucosal and GC cell lines. To further understand the potential mechanisms of the signature, Gene Set Enrichment Analysis (GSEA), pathway enrichment analysis, predictions of transcription factors (TFs)/miRNAs were performed.ResultsA novel EMT-related gene signature (including ITGAV, DAB2, SERPINE1, MATN3, PLOD2) was constructed for OS prediction of GC. With external validation, ROC curves indicated the signature's good performance. Patients stratified into high- and low-risk groups based on the signature yielded significantly different prognosis. Univariate and multivariate Cox regression suggested that the signature was an independent prognostic variable. Nomogram for prognostication including the signature presented better predictive accuracy and clinical usefulness than the similar model without risk score to some extent with external validation. The qRT-PCR assays suggested that high expression of the five EMT-related genes could be found in human GC cell lines compared with normal gastric mucosal cell line. GSEA and pathway enrichment analysis revealed that focal adhesion and ECM-receptor interaction might be the two important pathways to the signature.ConclusionOur EMT-related gene signature may have practical application as an independent prognostic factor in GC.

Dataset Information

Identification of a metabolic-related gene signature predicting the overall survival for patients with stomach adenocarcinoma.

Background

Methods

Results

Conclusions

Publications

Identification of a metabolic-related gene signature predicting the overall survival for patients with stomach adenocarcinoma.

Similar Datasets

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