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
Processing time: 125 Days and 19.4 Hours
ARTICLE HIGHLIGHTS
Research background

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

Research motivation

APC acts as a tumor suppressor gene in Wnt signal pathway, and mutation and inactivation of APC are unique key and early events in tumorigenesis, especially colorectal cancer. Compared with colorectal cancer, there have been much fewer studies on APC in other cancers. However, some successful studies have initially shown that APC could be used as a biomarker for GC. This inspired us to investigate the clinical features and mechanism of APC expression in GC.

Research objectives

The research objective was to validate that APC is associated with the pathogenesis and clinical features of GC. We demonstrated that high expression of APC is a biomarker for poor prognosis in T4 GC patient. Our research suggested that APC may be used as a novel biomarker for pathogenesis research, diagnosis, and treatment of GC.

Research methods

Based on RNA-Seq, miRNA-Seq, Illumina Infinium Human Methylation 450, and clinical follow-up data from TCGA, we systematically analyzed the APC-related mRNA and miRNA expression and DNA methylation profile on a genome-wide scale by multi-dimensional methods. The novel application of resource-sharing databases provided us with the opportunity to investigate more reliable biomarkers for GC.

Research results

We found that high expression of APC was a biomarker for poor prognosis in T4 GC patient. Our research brings new perspective to the APC gene in tumors, namely, APC is an oncogene in T4 GC patients and the high expression of APC indicates a poor prognosis in T4 GC patients. However, why high expression of APC predicts a poor prognosis only in T4 GC patients remains to be further studied.

Research conclusions

Our research demonstrated that APChigh may be a useful adverse prognostic biomarker for T4 GC patients. The finding that APChigh is associated with distinctive genome-wide gene/miRNA/methylation expression and related cellular functional pathways could well explain why APC acts as an adverse prognostic biomarker for T4 GC patients as well as the mechanism underlying its molecular biological function in GC.

Research perspectives

As a novel potential biological target, APC may be used to study the pathogenesis of GC and guide the clinical diagnosis, treatment, and prognosis evaluation of T4 GC patients.