Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2019; 25(37): 5590-5603
Published online Oct 7, 2019. doi: 10.3748/wjg.v25.i37.5590
Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer
Li Wei, Jing-Yun Wen, Jie Chen, Xiao-Kun Ma, Dong-Hao Wu, Zhan-Hong Chen, Jiang-Long Huang
Li Wei, Jing-Yun Wen, Jie Chen, Xiao-Kun Ma, Dong-Hao Wu, Zhan-Hong Chen, Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Jiang-Long Huang, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Huang JL and Chen ZH conceived and directed the entire study, and should be regarded as co-corresponding authors; Wei L designed the study and prepared the manuscript; Wen JY defined the intellectual content of the study; Wei L and Wen JY contributed equally to this study; Wu DH and Chen J participated in the literature research and clinical study; Wu DH and Ma XK conducted the experiments and data analysis; Chen J provided the statistical analysis; Wen JY, Huang JL, and Chen ZH revised the manuscript. All authors approved to submit the manuscript.
Institutional review board statement: This study was approved by the Scientific Committee of the Third Affiliated Hospital of Sun Yat-Sen University.
Institutional animal care and use committee statement: This study was approved by the Ethical Committee of the Third Affiliated Hospital of Sun Yat-Sen University.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The bioinformatic data could be downloaded from the public databases, and no additional data are available.
ARRIVE guidelines statement: This study 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: Jiang-Long Huang, MD, Associate Professor, Chief Doctor, Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Guangzhou 510630, Guangdong Province, China. drhjl@aliyun.com
Telephone: +86-20-85252228 Fax: +86-20-85252228
Received: July 30, 2019
Peer-review started: July 30, 2019
First decision: August 17, 2019
Revised: September 5, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: October 7, 2019
Processing time: 61 Days and 17.4 Hours
ARTICLE HIGHLIGHTS
Research background

Pancreatic cancer, called the king of cancer, contributes to high mortality rates. Drug resistance is a major concern to the treatment of pancreatic cancer, and the mechanism of the occurrence of drug resistance in pancreatic cancer is complex and still not clear. ADAM28 was previously reported as an oncogene in some cancers, but its role in pancreatic cancer is not clear, especially in the development of chemoresistance to gemcitabine.

Research motivation

To fully understand the role of gemcitabine in the development of chemoresistance to gemcitabine, and to discover a novel the therapeutic target for pancreatic cancer.

Research objectives

To explore the expression and significance of ADAM28 in pancreatic cancer, especially in the regulation of chemoresistance to gemcitabine.

Research methods

Bioinformatic analysis was performed to explore novel targets for the chemoresistance to gemcitabine in pancreatic cancer. RT-PCR and Western blot were used to study the expression of ADAM28. GEO and TCGA analyses were conducted to analyze the expression of ADAM28 in pancreatic cancer. Kaplan-Meier Plotter was used to show the OS and RFS rates of pancreatic cancer patients. Cell viability was performed by CCK-8 assay. GSEA was used to explore the ADAM28 and its co-expression network.

Research results

We first identified that ADAM28 was a novel gene that was involved in the regulation of chemoresistance to gemcitabine. We further analyzed the expression of ADAM28 and its significance in pancreatic cancer, indicating that ADAM28 could be a good biomarker to predict the prognosis. However, the detailed regulation mechanism of ADAM28 in pancreatic cancer needs further evaluation.

Research conclusions

ADAM28 is overexpressed in pancreatic cancer, and its overexpression contributes to gemcitabine chemoresistance. ADAM28 is an important mediator that participates in the regulation of chemoresistance-related signaling pathway. High expression of ADAM28 in pancreatic cancer can be used as a biomarker to predict the poor prognosis. ADAM28 might be a potential therapeutic target for overcoming chemoresistance to gemcitabine.

Research perspectives

Based on the bioinformatic analysis and in vitro experiments, ADAM28 was identified as a novel therapeutic target for pancreatic cancer, especially in the occurrence of drug resistance. In the future studies, an in-depth exploration of the ADAM28-mediated drug resistance signaling pathway will be very meaningful.