Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2018; 24(34): 3898-3907
Published online Sep 14, 2018. doi: 10.3748/wjg.v24.i34.3898
Low expression of CDK5RAP3 and DDRGK1 indicates a poor prognosis in patients with gastric cancer
Jian-Xian Lin, Xin-Sheng Xie, Xiong-Feng Weng, Chao-Hui Zheng, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Ping Li, Chang-Ming Huang
Jian-Xian Lin, Xin-Sheng Xie, Xiong-Feng Weng, Chao-Hui Zheng, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Ping Li, Chang-Ming Huang, Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
Jian-Xian Lin, Xin-Sheng Xie, Xiong-Feng Weng, Chao-Hui Zheng, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Ping Li, Chang-Ming Huang, Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
Jian-Xian Lin, Xin-Sheng Xie, Xiong-Feng Weng, Chao-Hui Zheng, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Ping Li, Chang-Ming Huang, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
Author contributions: Lin JX, Xie XS and Weng XF contributed equally to this article and should be considered co-first authors; Li P and Huang CM conceived and designed the study and are the co-corresponding authors; Lin JX, Xie XS and Weng XF performed the experiments; Zheng CH, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M and Tu RH analyzed and interpreted the data; Lin JX, Xie XS and Weng XF drafted the manuscript. All authors approved the final version of the article to be published.
Supported by the Science Foundation of the Fujian Province, China, No. 2018J01307; Startup Fund for Scientific Research, Fujian Medical University, No. 2016QH024; Scientific and Technological Innovation Joint Capital Projects of Fujian Province, No. 2016Y9031; Minimally Invasive Medical Center of Fujian Province, No. 2011708#; and the Young and Middle-aged Talent Training Project of the Fujian Provincial Health and Family Planning Commission, No. 2014-ZQNJC-13.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Fujian Medical University Union Hospital.
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 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/
Correspondence to: Chang-Ming Huang, MD, Doctor, Professor, Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou 350001, Fujian Province, China. hcmlr2002@163.com
Telephone: +86-591-83363366 Fax: +86-591-83363366
Received: May 19, 2018
Peer-review started: May 22, 2018
First decision: May 30, 2018
Revised: June 11, 2018
Accepted: June 25, 2018
Article in press: June 25, 2018
Published online: September 14, 2018
ARTICLE HIGHLIGHTS
Research background

Although the morbidity and mortality of the primary gastric cancer has declined in recent decades, it is still the third most common cause of cancer-related deaths worldwide. The symptoms of early gastric cancer are not highly specific. Therefore, misdiagnosis and missed diagnosis may occur. Therefore, finding new biomarkers will help to improve earlier diagnosis and treatment of gastric cancer. In recent years, an increasing number of studies on the prognostic indicators of gastric cancer have been published. However, the expression of CDK5RAP3 and DDRGK1 in gastric cancer and its influence on prognosis have not yet been reported.

Research motivation

At present, the etiology and pathogenesis of gastric cancer has not yet been fully clarified. There is also a lack of specific and highly effective therapeutic drugs available for use in clinical practice. The symptom specificity of early gastric cancer is not obvious, so most patients are already in advanced stages before receiving medical treatment, which seriously affects the prognosis of patients. Therefore, searching for molecular markers that can be used as an independent prognostic factor for gastric cancer is of great significance for the early diagnosis and targeted treatment of gastric cancer. A series of studies on tumor prognostic factors is expected to provide a new target for the treatment of gastric cancer while providing new targets for the treatment of gastric cancer. The expression of CDK5RAP3 and DDRGK1 in gastric cancer and their influence on clinicopathological characteristics and prognosis have not previously been discussed.

Research objectives

The aim of this study is to identify novel effective biomarkers to classify patients with low or high survival. This would provide a guide to clinicians to select therapeutic strategies for patients and provide personalized therapy according to the predicted survival rate. In this study, we investigated two interacting proteins, CDK5RAP3 and DDRGK1, which may help determine patient management strategies.

Research methods

We used immunohistochemistry to detect the expression of CDK5RAP3 and DDRGK1 in gastric cancer and adjacent tissues. Western Blot was used to detect the expression of CDK5RAP3 and DDRGK1 in gastric cancer and its adjacent tissues and cell lines. According to immunohistochemistry scores, the patients were divided into CDK5RAP3 high expression group and CDK5RAP3 low expression group, DDRGK1 high expression group and DDRGK1 low expression group, and the relationship between the expression level and clinicopathological data was analyzed. Furthermore, based on the combined expression of CDK5RAP3 and DDRGK1, we classified the patients into three subtypes: CDK5RAP3 and DDRGK1 high (n = 9), CDK5RAP3 or DDRGK1 low (n = 45) and CDK5RAP3 and DDRGK1 low (n = 81). Then, we used the Kaplan-Meier method to analyze the effect of different expression patterns on prognosis.

Research results

Our research found that the expression of CDK5RAP3 and DDRGK1 was down-regulated in gastric cancer. Low expression of CDK5RAP3 or DDRGK1 is a poor prognostic factor for gastric cancer patients. Moreover, prognostic analysis showed that the co-expression of CDK5RAP3 and DDRGK1 was an independent prognostic factor correlating with the overall survival of gastric cancer patients. Combined expression analysis of CDK5RAP3 and DDRGK1 may provide a more accurate prognostic value for overall survival. This study presents two interacting proteins, which may be useful to determine patient management strategies. These makers may predict the prognosis of gastric cancer patients through an analysis of CDK5RAP3 and DDRGK1 protein expression in preoperative biopsy and tumor specimens.

Research conclusions

This study found that low expression of CDK5RAP3 and DDRGK1 are closely related to the poor prognosis of gastric cancer patients, and the co-expression of CDK5RAP3 and DDRGK1 is an independent prognostic factor correlated with the overall survival of gastric cancer patients. These two interacting proteins, CDK5RAP3 and DDRGK1, may be helpful in determining patient management strategies, and to predict the prognosis of gastric cancer patients.We hypothesized that CDK5RAP3 and DDRGK1 were key genes which may participate in the biological regulation of gastric cancer. The mechanism of their role in gastric cancer has not been fully elucidated and further studies are needed. With advances in technology, humans may find more effective and new indicators in the future to guide treatment, improve prognosis, and reduce the recurrence rate and mortality of patients with gastric cancer.

Research perspectives

This study found the prognostic value of two interacting proteins, CDK5RAP3 and DDRGK1, by detecting the expression of both in clinical specimens, combined with detailed clinicopathological data analysis. This study provided ideas for finding new tumor prognosis related molecules. Manipulation of both CDK5RAP3 and DDRGK1 expression in different gastric cancer cell lines, such as overexpression or knockdown, will be needed for future research. Further study is necessary to investigate the characteristics of cancer cells and explore the mechanism of CDK5RAP3 and DDRGK1 affecting the development of gastric cancer by an in vitro cell model and in vivo xenograft model.