Jahantab Mohammad Bagher, Salehi Mohammad, Koushki Mehdi, Farrokhi Yekta Reyhaneh, Amiri-Dashatan Nasrin, Rezaei-Tavirani Mostafa
Clinical Research Development Unit, Shahid Jalil Hospital, Yasuj University of Medical Sciences, Yasuj, Iran.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Rep Biochem Mol Biol. 2024 Jul;13(2):281-300. doi: 10.61186/rbmb.13.2.281.
Gastric cancer (GC) is a prevalent malignancy with high recurrence. Advances in systems biology have identified molecular pathways and biomarkers. This study focuses on discovering gene and miRNA biomarkers for diagnosing and predicting survival in GC patients.
Three sets of genes (GSE19826, GSE81948, and GSE112369) and two sets of miRNA expression (GSE26595, GSE78775) were obtained from the Gene Expression Omnibus (GEO), and subsequently, differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Functional pathway enrichment, DEG-miR-TF-protein-protein interaction network, DEM-mRNA network, ROC curve, and survival analyses were performed. Finally, qRT-PCR was applied to validate our results.
From the high-throughput profiling studies of GC, we investigated 10 candidate mRNA and 7 candidate miRNAs as potential biomarkers. Expression analysis of these hubs revealed that 5 miRNAs (including miR-141-3p, miR-204-5p, miR-338-3p, miR-609, and miR-369-5p) were significantly upregulated compared to the controls. The genes with the highest degree included 6 upregulated and 4 downregulated genes in tumor samples compared to controls. The expression of miR-141-3p, miR-204-5p, SESTD1, and ANTXR1 were verified in vitro from these hub DEMs and DEGs. The findings indicated a decrease in the expression of miR-141-3p and miR-204-5p and increased expression of SESTD1 and ANTXR1 in GC cell lines compared to the GES-1 cell line.
The current investigation successfully recognized a set of prospective miRNAs and genes that may serve as potential biomarkers for GC's early diagnosis and prognosis.
胃癌（GC）是一种常见的恶性肿瘤，复发率高。系统生物学的进展已经确定了分子途径和生物标志物。本研究专注于发现用于诊断和预测GC患者生存的基因和miRNA生物标志物。
从基因表达综合数据库（GEO）中获取了三组基因（GSE19826、GSE81948和GSE112369）和两组miRNA表达数据（GSE26595、GSE78775），随后鉴定了差异表达基因（DEGs）和miRNA（DEMs）。进行了功能途径富集、DEG-miR-TF-蛋白质-蛋白质相互作用网络、DEM-mRNA网络、ROC曲线和生存分析。最后，应用qRT-PCR验证我们的结果。
通过对GC的高通量分析研究，我们调查了10个候选mRNA和7个候选miRNA作为潜在生物标志物。对这些核心分子的表达分析表明，与对照组相比，5个miRNA（包括miR-141-3p、miR-204-5p、miR-338-3p、miR-609和miR-369-5p）显著上调。与对照组相比，肿瘤样本中连接度最高的基因包括6个上调基因和4个下调基因。从这些核心DEM和DEG中体外验证了miR-141-3p、miR-204-5p、SESTD1和ANTXR1的表达。结果表明，与GES-1细胞系相比，GC细胞系中miR-141-3p和miR-204-5p的表达降低，SESTD1和ANTXR1的表达增加。
当前研究成功识别出一组可能作为GC早期诊断和预后潜在生物标志物的前瞻性miRNA和基因。
