Pang L, Yan X, Su D
Department of Gastroenterology, Nanning Second People's Hospital, Nanning, China.
Department of Endocrinology, Nanning Second People's Hospital, Nanning, China.
J Physiol Pharmacol. 2021 Dec;72(6). doi: 10.26402/jpp.2021.6.09. Epub 2022 Apr 24.
This study aimed to screen the potential candidate genes and relevant biological markers associated with gastrointestinal metaplasia that progresses to gastric cancer (GIM-GC). Microarray datasets (GSE78523) were downloaded from the GEO database. Differentially expressed genes (DEGs) between GIM-GC samples and healthy controls were identified. GO and KEGG pathway enrichment analyses were performed. STRING and Cytoscape were used to identify significant module and hub genes. Survival analysis was applied to identify key genes. A Venn diagram was built to find hub DEGs that differed in all three relevant comparisons (GIM-GC vs. healthy controls vs. GIM-NoGC). The clinical characteristics of the hub DEGs were evaluated using the Cancer Genome Atlas dataset. The study found 257 DEGs (217 upregulated and 40 downregulated). The upregulated DEGs were enriched in regulation of microvillus length and phospholipid binding and were components of the apical plasma membrane. Downregulated DEGs were involved in digestion and hormone activity and were found in the extracellular space. Fat digestion and absorption as well as gastric acid secretion were the pathways enrichment. The most important gene modules related mainly to O-glycan processing, extracellular exosome, hormone activity, and vitamin and fat digestion and absorption. Eleven hub genes were identified, of which APOB, FABP1, CDX2, GCG, HNF4A, SLC26A3, CFTR, MUC5AC, OLFM4, and SI were related to the prognosis. Olfactomedin-4 (OLFM4) was the most relevant DEG to identify GIM-GC. In conclusion: DEGs and hub genes are helpful to understand the molecular mechanisms of GIM-GC. OLFM4 may be a biological marker for GIM-GC.
本研究旨在筛选与进展为胃癌的胃肠化生（GIM-GC）相关的潜在候选基因和相关生物学标志物。从基因表达综合数据库（GEO数据库）下载了微阵列数据集（GSE78523）。鉴定了GIM-GC样本与健康对照之间的差异表达基因（DEG）。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。使用STRING和Cytoscape软件来识别显著模块和枢纽基因。应用生存分析来鉴定关键基因。构建维恩图以找出在所有三个相关比较（GIM-GC与健康对照与非GC的GIM）中均不同的枢纽DEG。使用癌症基因组图谱数据集评估枢纽DEG的临床特征。该研究发现了257个DEG（217个上调和40个下调）。上调的DEG在微绒毛长度调节和磷脂结合中富集，并且是顶端质膜的组成部分。下调的DEG参与消化和激素活性，并且存在于细胞外空间。脂肪消化与吸收以及胃酸分泌是富集的通路。最重要的基因模块主要与O-聚糖加工、细胞外外泌体、激素活性以及维生素和脂肪消化与吸收有关。鉴定出11个枢纽基因，其中载脂蛋白B（APOB）、脂肪酸结合蛋白1（FABP1）、尾型同源盒转录因子2（CDX2）、胰高血糖素（GCG）、肝细胞核因子4α（HNF4A）、溶质载体家族26成员3（SLC26A3）、囊性纤维化跨膜传导调节因子（CFTR）、粘蛋白5AC（MUC5AC）、嗅觉介质4（OLFM4）和蔗糖酶异麦芽糖酶（SI）与预后相关。嗅觉介质4（OLFM4）是识别GIM-GC最相关的DEG。总之：DEG和枢纽基因有助于理解GIM-GC的分子机制。OLFM4可能是GIM-GC的生物学标志物。
