Evaluation of MT Family Isoforms as Potential Biomarker for Predicting Progression and Prognosis in Gastric Cancer

Author:

Tong Mingfu1,Lu Wenquan2,Liu Hao3,Wu Jian3,Jiang Mingzuo3,Wang Xin3,Hao Jianyu1ORCID,Fan Daiming13ORCID

Affiliation:

1. Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

2. Department of Gastroenterology, First Affiliated Hospital, Zhengzhou University, Henan, Zhengzhou 450000, China

3. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China

Abstract

Background. 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. Methods. 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. Results. 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. Conclusion. 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.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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