Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2019; 25(31): 4452-4467
Published online Aug 21, 2019. doi: 10.3748/wjg.v25.i31.4452
High expression of APC is an unfavorable prognostic biomarker in T4 gastric cancer patients
Wei-Bo Du, Chen-Hong Lin, Wen-Biao Chen
Wei-Bo Du, Chen-Hong Lin, Wen-Biao Chen, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Chen WB designed and supervised the research; Du WB, Lin CH, and Chen WB interpreted the data; Du WB wrote the manuscript; Lin CH constructed the figures and tables; Chen WB revised the manuscript.
Supported by the Major National S&T Projects for Infectious Diseases, No. 2018ZX10301401-005; the National Key Research and Development Program of China, No. 2018YFC2000500; the Key Research and Development Plan of Zhejiang Province, No. 2019C04005; and the National Natural Science Foundation of China, No. 81571953.
Institutional review board statement: The study was approved by the Clinical Research Ethics Committee of College of Medicine, Zhejiang University.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: All research data can be downloaded from public databases.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Wen-Biao Chen, PhD, Doctor, Postdoctoral Fellow, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University. No. 79, Qingchun Road, Hangzhou 310003, Zhejiang Province, China. chenwenbiao@sina.com
Telephone: +86-18320993293 Fax: +86-571-87236114
Received: April 18, 2019
Peer-review started: April 18, 2019
First decision: June 16, 2019
Revised: July 18, 2019
Accepted: August 7, 2019
Article in press: July 19, 2019
Published online: August 21, 2019
Abstract
BACKGROUND

Adenoma polyposis coli (APC) mutation is associated with tumorigenesis via the Wnt signaling pathway.

AIM

To investigate the clinical features and mechanism of APC expression in gastric cancer (GC).

METHODS

Based on APC expression profile, the related genome-wide mRNA expression, microRNA (miRNA) expression, and methylation profile in GC, the relationship between APC and GC, as well as the prognostic significance of APC were systematically analyzed by multi-dimensional methods.

RESULTS

We found that high expression of APC (APChigh) was significantly associated with adverse outcomes of T4 GC patients. Genome-wide gene expression analysis revealed that varying APC expression levels in GC were associated with some important oncogenes, and corresponding cellular functional pathways. Genome-wide miRNA expression analysis indicated that most of miRNAs associated with high APC expression were downregulated. The mRNA-miRNA regulatory network analysis revealed that down-regulated miRNAs affected their inhibitory effect on tumor genes. Genome-wide methylation profiles associated with APC expression showed that there was differential methylation between the APChigh and APClow groups. The number of hypermethylation sites was larger than that of hypomethylation sites, and most of hypermethylation sites were enriched in CpG islands.

CONCLUSION

Our research demonstrated that high APC expression is an unfavorable prognostic factor for T4 GC patients and may be used as a novel biomarker for pathogenesis research, diagnosis, and treatment of GC.

Keywords: Adenoma polyposis coli, Gastric cancer, Prognosis, mRNA, miRNA, Methylation

Core tip: We found that high expression of adenoma polyposis coli (APC) was associated with a poor prognosis in T4 gastric cancer (GC) patients. There was differential expression of mRNAs and miRNAs as well as differential DNA methylation between the high expression of APC (APChigh) and low expression of APC (APClow) groups. The link between APChigh and differential expression of mRNAs, miRNAs, and DNA methylation may contribute to the poor prognosis in T4 GC patients, and be involved in the pathogenesis of GC. APC could be used as a novel biomarker for clinical diagnosis, therapy, and assessment of prognosis in T4 GC patients, as well as for further research of the pathogenesis of GC.