Fattahi Sadegh, Nikbakhsh Novin, Taheri Hassan, Ranaee Mohammad, Akhavan-Niaki Haleh
Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Rep Biochem Mol Biol. 2021 Jan;9(4):478-489. doi: 10.52547/rbmb.9.4.478.
Gastric cancer is among the most common cancers worldwide that currently lacks effective diagnostic biomarkers and therapeutic targets. Next-generation RNA sequencing is a powerful tool that allows rapid and accurate transcriptome-wide profiling to detect differentially expressed transcripts involved in normal biological and pathological processes. Given the function of this technique, it has the potential to identify new molecular targets for the early diagnosis of disease, particularly in gastric adenocarcinoma.
In this study, whole-transcriptome analysis was performed with RNA sequencing on tumoral and non-tumoral tissue samples from patients with early-stage gastric cancer. Gene ontology and pathway enrichment analysis were used to determine the main function of the specific genes and pathways present in tissue samples.
Analysis of the differentially expressed genes revealed 5 upregulated and 234 downregulated genes in gastric cancer tissues. Pathway enrichment analysis revealed significantly dysregulated signalling pathways, including those involved in gastric acid secretion, drug metabolism and transporters, molecular toxicology, O-linked glycosylation of mucins, immunotoxicity, metabolism of xenobiotics by cytochrome P450, and glycosylation. We also found novel downregulated non-coding RNAs present in gastric cancer tissues, including GATA6 antisense RNA 1, antisense to LYZ, antisense P4HB, overlapping ACER2, long intergenic non-protein coding RNA 2688 (LINC02688) and uncharacterized LOC25845 (PP7080).
The transcriptomic data found in this study illustrates the power of RNA-sequencing in discovering novel genes and tumorigenic pathways involved in human carcinogenesis. The anomalies present in these genes may serve as promising tools for the development of accurate diagnostic biomarkers for the detection of early-stage gastric cancer.
胃癌是全球最常见的癌症之一，目前缺乏有效的诊断生物标志物和治疗靶点。下一代RNA测序是一种强大的工具，可实现快速、准确的全转录组分析，以检测参与正常生物学和病理过程的差异表达转录本。鉴于该技术的功能，它有潜力识别疾病早期诊断的新分子靶点，尤其是在胃腺癌中。
在本研究中，对早期胃癌患者的肿瘤组织和非肿瘤组织样本进行了RNA测序全转录组分析。基因本体和通路富集分析用于确定组织样本中特定基因和通路的主要功能。
差异表达基因分析显示，胃癌组织中有5个基因上调，234个基因下调。通路富集分析显示信号通路明显失调，包括胃酸分泌、药物代谢和转运、分子毒理学、粘蛋白O-连接糖基化、免疫毒性、细胞色素P450对外源化合物的代谢以及糖基化相关通路。我们还发现胃癌组织中存在新的下调非编码RNA，包括GATA6反义RNA 1、LYZ反义RNA、P4HB反义RNA、重叠ACER2、长链基因间非编码RNA 2688（LINC02688）和未表征的LOC25845（PP7080）。
本研究中发现的转录组数据说明了RNA测序在发现参与人类致癌作用的新基因和致瘤途径方面的强大作用。这些基因中存在的异常可能成为开发用于检测早期胃癌的准确诊断生物标志物的有前途的工具。
