Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics anal
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RESEARCH ARTICLE
Open Access
Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis Zhenhua Yin1†, Dejun Wu2†, Jianping Shi1†, Xiyi Wei3, Nuyun Jin1, Xiaolan Lu1* and Xiaohan Ren3*
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. Keywords: Bioinformatics analysis, Prognosis, ALDH3A2, Immune cells
Background GC arises from the epithelial cells of the gastric mucosa and is a common malignancy of the digestive system that results in an estimated 990,000 new cases and 738,000 deaths each year [1]. The onset of GC can be seen at any age but is typically more common in men with an * Correspondence: [email protected]; [email protected] † Zhenhua Yin, Dejun Wu and Jianping Shi contributed equally to this work. 1 Department of Digestive, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai 201399, China 3 The State Key Lab of Reproductive, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China Full list of author information is available at the end of the article
approximately 2:1 male-to-female ratio [1]. Approximately 90% of GC are adenocarcinomas (STAD; stomach adenocarcinomas), of which the two most frequent histological subtypes are classified as well-differentiated (or intestinal type) and undifferentiated (or diffuse type). GC is known to be a multifactorial disease, and the incidence of GC is associated with a range of factors, including helicobacter pylori infection, dietary factors, tobacco, obesity, and others
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