Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis

Abstract

Background: Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further.Methods: In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database.Results: Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4.Conclusion: We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.

Identification of the Immune Cell Infiltration Landscape in Head and Neck Squamous Cell Carcinoma (HNSC) for the Exploration of Immunotherapy and Prognosis

“…Based on the univariate COX regression and multivariate COX regression analysis, we fnally obtain the genes that are closely associated with the prognosis of HNSC patients, which includes ZAP70 and IGKV2D-40. In recent years, many studies focused on bioinformatics analysis to explore the genes that play an important role in the prognosis of tumor patients [21][22][23][24][25]. Tere was a correlation between nivolumab response and HNCAF-0/3 of fbroblast subtypes, whereas HNCAF-1 caused immunosuppression [26].…”

Cancer-Associated Fibroblasts Affect Tumor Metabolism and Immune Microenvironment in Gastric Cancer and Identification of Its Characteristic Genes

“…In medical research, the investigation and analysis of the classifcation or prediction of response variables in biomedical research are often challenging due to the data sparsity generated by limited sample sizes and a moderate or very large number of predictors. Bioinformatic analysis can efectively solve this contradiction and is a powerful tool for screening clinical predictors [16].…”

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

“…For instance, gene set enrichment analysis and IHC results indicate that high ALDH3A2 expression is associated with superior OS of GC patients. Moreover, ALDH3A2 is negatively correlated with immune checkpoints, including cytotoxic T‐lymphocyte‐associated antigen 4, programmed cell death protein 1 in immune cells, and its ligand PD‐L2 in GC cells 198 . More recently, Antonowicz et al.…”

“…Moreover, ALDH3A2 is negatively correlated with immune checkpoints, including cytotoxic Tlymphocyte-associated antigen 4, programmed cell death protein 1 in immune cells, and its ligand PD-L2 in GC cells. 198 More recently, Antonowicz et al supported that the loss of ALDH3A2 expression is linked to malignant transformation and progression and is associated with poorer survival in esophageal adenocarcinoma. 199 Surprisingly, ALDH3A2 represents a very intriguing isoform as its expression is downregulated but increased in response to various treatment trials in PCa.…”