Department of Digestive, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai, 201399, China.
Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai, 201399, China.
BMC Cancer. 2020 Nov 4;20(1):1062. doi: 10.1186/s12885-020-07493-x.
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.
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.
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.
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.
大量研究表明，基因在肿瘤的发生和生长中起着关键作用。然而，基因表达在胃癌（GC）中的潜在作用仍有待进一步研究。
本研究通过比较基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中的肿瘤组织与相邻正常组织，鉴定重叠差异表达基因（DEGs）。
我们的分析确定了 79 个上调和 10 个下调基因。对鉴定出的基因进行功能富集分析和预后分析，选择脂肪酸醛脱氢酶（FALDH）基因 ALDH3A2 进行更详细的分析。我们进行了基因集富集分析（GSEA）和免疫相关性分析（浸润、拷贝数改变和检查点），以深入阐明 ALDH3A2 的作用机制。基于 140 例石蜡包埋人 GC 样本的免疫组化（IHC）结果表明，ALDH3A2 在低级别 GC 病例中过表达，并且 ALDH3A2 低表达的患者的 OS 明显短于 ALDH3A2 高表达的患者。体外结果表明，ALDH3A2 的表达与 PDCD1、PDCD1LG2 和 CTLA-4 呈负相关。
我们得出结论，ALDH3A2 可能是 GC 缓解和免疫治疗的潜在参考值，也是 GC 预后的独立预测标志物。
