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The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

ABSTRACT: Drug metabolism-associated genes have been clarified to play a vital role in the process of cancer cell growth and migration. Nevertheless, the correlation between drug metabolism-associated genes and gastric cancer (GC) has not been fully explored and clarified. This paper has focused on the role of aldehyde dehydrogenase 6 family member A1 (ALDH6A1), a drug metabolism-associated gene, in the immune regulation and prognosis of GC patients. Using several bioinformatics platforms and immunohistochemistry (IHC) assay, we found that ALDH6A1 expression was significantly down-regulated in GC tissues. Moreover, higher expression of ALDH6A1 was related to the better prognosis of GC patients. ALDH6A1 was also found to be involved in the regulation of several immune-associated signatures, including immunoinhibitors. In conclusion, the above results have concluded that aberrant expression of ALDH6A1 might be served as the promising predictor for prognosis and clinical immunotherapy response in GC patients.

SUBMITTER: Cai Y

PROVIDER: S-EPMC9512493 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

Cai Yuan Y Zeng Rong R Peng Jinwu J Liu Wei W He Qingchun Q Xu Zhijie Z Bai Ning N

Aging 20220912 17

Drug metabolism-associated genes have been clarified to play a vital role in the process of cancer cell growth and migration. Nevertheless, the correlation between drug metabolism-associated genes and gastric cancer (GC) has not been fully explored and clarified. This paper has focused on the role of aldehyde dehydrogenase 6 family member A1 (ALDH6A1), a drug metabolism-associated gene, in the immune regulation and prognosis of GC patients. Using several bioinformatics platforms and immunohistoc ...[more]

PMID: 36098688

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Project description:BackgroundThis study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients.MethodsIn this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes.ResultsInitially, we identified DE-NMRGs involved in NAD biosynthesis, with seven (DNAJB13, CST2, THPO, CIDEA, ONECUT1, UPK1B and SNCG) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples.ConclusionIn this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.

Project description:BackgroundPlatelets can dynamically regulate tumor development and progression. Nevertheless, research on the predictive value and specific roles of platelets in gastric cancer (GC) is limited. This research aims to establish a predictive platelets-related gene signature in GC with prognostic and therapeutic implications.MethodsWe downloaded the transcriptome data and clinical materials of GC patients (n=378) from The Cancer Genome Atlas (TCGA) database. Prognostic platelets-related genes screened by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model. Kaplan-Meier curves and receiver operating characteristic curves (ROCs) were performed in the TCGA cohort and three independent validation cohorts. A nomogram integrating the risk score and clinicopathological features was constructed. Functional enrichment and tumor microenvironment (TME) analyses were performed. Drug sensitivity prediction was conducted through The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR).ResultsA ten-gene (SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF) predictive risk model was finally constructed. Patients were categorized as high- or low-risk using median risk score as the threshold. The area under the ROC curve (AUC) values for the 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis showed a better OS in low-risk patients in the training and validation cohorts. The AUCs of the nomogram for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analyses revealed a higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750.ConclusionThe novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.

Dataset Information

The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

Publications

The downregulated drug-metabolism related ALDH6A1 serves as predictor for prognosis and therapeutic immune response in gastric cancer.

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