Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Department of Gastroenterology, First Affiliated Hospital, Zhengzhou University, Henan, Zhengzhou 450000, China.
Biomed Res Int. 2019 Jul 17;2019:2957821. doi: 10.1155/2019/2957821. eCollection 2019.
Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear.
Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC.
Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients.
MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.
金属硫蛋白（MTs）家族包含许多同工型，其中大多数在广泛的癌症中经常失调。然而，对于每个独特的 MT 家族同工型，其表达模式和确切作用如何促进胃癌（GC）的发生、进展和耐药性仍然不清楚。
利用 Oncomine、基因表达谱交互式分析（GEPIA）、Kaplan-Meier 绘图器、SurvExpress、MethHC、cBioportal 和 GeneMANIA 等公共数据库进行综合生物信息学分析，并尝试检测每个 MT 家族成员与 GC 之间的基本关系。
生物信息学数据表明，与正常胃组织相比，GC 中所有 MT 家族成员的 mRNA 表达几乎都较低（P<0.05），并且每个 MT 成员 mRNA 表达降低的患者的预后价值（OS、FP、PPS）不一致，这取决于 MT 的个体同工型。从 MethHC 数据库中检测到大多数 MT 成员启动子区域的甲基化与它们的 mRNA 表达呈负相关（p<0.001）。从 TCGA 下载的数据显示，GC 患者中 MTs 很少发生突变，而 MT2A 在 GC 患者中经常受到其他三个基因（FOS、JUN、SP1）的调控。
MTs 在 GC 患者中几乎下调，并且不同类型的 MT 在 GC 患者中具有不同的预后作用。MTs 基因启动子区域的甲基化部分导致其在 GC 中表达降低。我们从多个独立数据库进行的综合分析可能会进一步促使研究人员探索针对 MT 的靶向试剂或 GC 患者的潜在诊断和预后标志物。
