Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6119-6127
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6119
Aberrant DNA-PKcs and ERGIC1 expression may be involved in initiation of gastric cancer
Fu-Rong Wang, Yu-Cai Wei, Zhi-Jian Han, Wen-Ting He, Xiao-Ying Guan, Hao Chen, Yu-Min Li
Fu-Rong Wang, Yu-Min Li, School of Life Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
Fu-Rong Wang, Xiao-Ying Guan, Department of Pathology, Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Yu-Cai Wei, Hao Chen, Yu-Min Li, Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Zhi-Jian Han, Wen-Ting He, The Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Author contributions: Wang FR and Wei YC contributed equally to this study; Wang FR, Wei YC and Li YM designed the research; Wang FR, Wei YC, Han ZJ , He WT and Guan XY performed the research; Han ZJ and He WT contributed new reagents or analytic tools; Wang FR and Guan XY analyzed the data; Wang FR, Wei YC and Li YM wrote the paper.
Supported by National Natural Science Foundation of China, No. 31270532 and No. 81670594.
Institutional review board statement: This study was approved by the Second Hospital of Lanzhou University.
Informed consent statement: All specimens from the patients were taken after informed consent and ethical permission were obtained for participation in the study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Dr. Yu-Min Li, Professor, Department of General Surgery, Second Hospital of Lanzhou University, 82 Cuiyingmen, Lanzhou 730000, Gansu Province, China. liym@lzu.edu.cn
Received: March 30, 2017
Peer-review started: April 8, 2017
First decision: May 12, 2017
Revised: June 14, 2017
Accepted: August 1, 2017
Article in press: August 2, 2017
Published online: September 7, 2017
Abstract
AIM

To investigate the molecular mechanisms of gastric carcinogenesis.

METHODS

We used label-free quantification technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in 160 specimens of normal gastric mucosa, gastric mucosa with mild dysplasia, moderate dysplasia, severe dysplasia, and early mucosal gastric cancer (GC) collected at the Second Hospital of Lanzhou University from 2010 to 2015. Immunohistochemistry was used to verify the differentially expressed proteins detected by LC-MS/MS.

RESULTS

With a threshold of a 1.2-fold change and a P-value < 0.05 between mild dysplasia, moderate dysplasia, severe dysplasia or early mucosal GC and matched normal gastric mucosa tissues, proteomic analysis identified 365 significantly differentially expressed proteins. ERGIC1 expression decreased, while DNA-PKcs expression increased gradually along with different stages of GC initiation based on the tendency of fold change. The expression patterns of ERGIC1 and DNA-PKcs revealed by immunohistochemistry were consistent with the LC-MS/MS results.

CONCLUSION

The results suggest that aberrant ERGIC1 and DNA-PKcs expression may be involved in GC initiation.

Keywords: DNA-PKcs, ERGIC1, Dysplasia, Proteomics, Gastric cancer

Core tip: Using label-free combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), the expression of 365 proteins based on the tendency of fold change was revealed to be statistically different between the various stages of gastric cancer (GC) initiation. Furthermore, we observed that ERGIC1 expression decreased, while DNA-PKcs expression increased gradually along with different stages of GC initiation based on the tendency of fold change. The expression patterns of ERGIC1 and DNA-PKcs revealed by immunohistochemistry were consistent with the LC-MS/MS results. These data indicate that abnormal ERGIC1 and DNA-PKcs expression may play an important role in GC initiation.