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转录组分析揭示 SALL4 是胃腺癌的一个预后关键基因。

Transcriptome analysis reveals SALL4 as a prognostic key gene in gastric adenocarcinoma.

机构信息

Department of Biotechnology, Mizoram University, Aizawl, Mizoram, 796 004, India.

Director, Zoram Medical College, Falkawn, Mizoram, 796005, India.

出版信息

J Egypt Natl Canc Inst. 2022 Mar 14;34(1):11. doi: 10.1186/s43046-022-00108-5.

Abstract

BACKGROUND

Stomach adenocarcinoma (STAD) dominates 80-90% of gastric cancer (GC). Over the years, it has been realized that the identification of the genes responsible for gastric carcinogenesis is essential to understand the biomarker discovery.

METHODS

This study aims to identify candidate genes for biomarker discovery in STAD. RNA-Seq was performed on three paired tumor-normal and one unpaired tumor samples from four GC patients and investigated for differentially expressed genes (DEGs) using DESeq2. Gene set enrichment analysis were performed. The DEGs were compared with two STAD microarray datasets available on Gene Expression Omnibus (GEO) database. Survival study (OS) were performed using KM-Plotter on the common genes between all the datasets.

RESULTS

Totally, 148 DEGs were identified, wherein 55 genes were upregulated and 93 genes were downregulated with |log2foldchange| > 1 and Benjamini-Hochberg (BH) Adjusted P value < 0.01. Cell adhesion molecule (CAM) Pathway was found to be the most significant among the upregulated genes. Gastric acid secretion and mineral absorption pathways were the most significant pathways among the downregulated genes. Comparison with two GEO datasets followed by OS analysis revealed two upregulating genes, APOC1 and SALL4 with prognostic significance.

CONCLUSION

Upregulation of APOC1 is associated with marginal overall survival (OS) and SALL4 over-expression was associated with the poor OS using KM-Plotter during 5 years data period. Our study suggests that SALL4 could be a promising biomarker candidate in STAD.

摘要

背景

胃腺癌(STAD)占胃癌(GC)的 80-90%。多年来,人们已经意识到,确定导致胃发生癌变的基因对于理解生物标志物的发现至关重要。

方法

本研究旨在鉴定 STAD 中用于生物标志物发现的候选基因。对来自 4 名 GC 患者的三对肿瘤-正常组织和一对非配对肿瘤样本进行 RNA-Seq,并使用 DESeq2 研究差异表达基因(DEG)。进行基因集富集分析。将 DEG 与两个可从基因表达综合数据库(GEO)获得的 STAD 微阵列数据集进行比较。使用 KM-Plotter 在所有数据集之间进行常见基因的生存研究(OS)。

结果

总共鉴定出 148 个 DEG,其中 55 个基因上调,93 个基因下调,|log2foldchange|>1,Benjamini-Hochberg(BH)调整后的 P 值<0.01。上调基因中细胞黏附分子(CAM)途径最为显著。下调基因中胃酸分泌和矿物质吸收途径最为显著。与两个 GEO 数据集进行比较后,进行 OS 分析显示,两个上调基因 APOC1 和 SALL4 具有预后意义。

结论

APOC1 的上调与边缘总生存期(OS)相关,SALL4 的过表达与 KM-Plotter 在 5 年数据期间的不良 OS 相关。我们的研究表明,SALL4 可能是 STAD 中一种有前途的生物标志物候选物。

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