Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2015; 21(27): 8398-8407
Published online Jul 21, 2015. doi: 10.3748/wjg.v21.i27.8398
SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis
Chao-Jie Wang, Zi-Zhen Zhang, Jia Xu, Ming Wang, Wen-Yi Zhao, Lin Tu, Chun Zhuang, Qiang Liu, Yan-Yin Shen, Hui Cao, Zhi-Gang Zhang
Chao-Jie Wang, Zi-Zhen Zhang, Jia Xu, Ming Wang, Wen-Yi Zhao, Lin Tu, Chun Zhuang, Hui Cao, Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Qiang Liu, Yan-Yin Shen, Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Chao-Jie Wang, Zhi-Gang Zhang, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
Author contributions: Wang CJ and Zhang ZZ contributed equally to this study and were co-first authors; Wang CJ and Zhang ZZ participated in data collection, data analysis, and wrote the manuscript; Xu J, Wang M, Zhao WY, Tu L, Zhuang C, Liu Q, and Shen YY participated in data collection and helped perform the statistical analysis; Cao H and Zhang ZG conceived the study, participated in its design, and provided critical revisions; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China General Program, No. 81272743; Shanghai City Committee of Science and Technology Key Project, No. 11411950800; and Key Discipline Project of Renji Hospital, Shanghai Jiaotong University School of Medicine, No. RJ4101304.
Institutional review board statement: Clinical materials and samples were obtained with approval from the Ethical Committees of Renji Hospital and Shanghai Jiaotong University School of Medicine.
Clinical trial registration statement: The clinical investigation was carried out in accordance with the principles expressed in the Declaration of Helsinki.
Informed consent statement: Written informed consent was obtained from all participants.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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: Hui Cao, MD, Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 1630 Dong fang Road, Shanghai 200127, China. caohuishcn@hotmail.com
Telephone: +86-21-68383711 Fax: +86-21-58394262
Received: November 25, 2014
Peer-review started: November 26, 2014
First decision: January 8, 2015
Revised: February 13, 2015
Accepted: April 28, 2015
Article in press: April 28, 2015
Published online: July 21, 2015
Abstract

AIM: To assess the influence of SLIT and NTRK-like family member 3 (SLITRK3) on the prognosis of gastrointestinal stromal tumor (GIST) and determine whether SLITRK3 can help improve current risk stratification systems.

METHODS: We hypothesized that SLITRK3 could be used as a prognostic molecular biomarker for GIST. 35 fresh tumor samples and 417 paraffin-embedded specimens from GIST patients were utilized. SLITRK3 mRNA expression in GIST tumor tissue was detected by real-time polymerase chain reaction, and SLITRK3 protein levels were estimated by immunohistochemistry. The correlation of SLITRK3 expression with various tumor clinicopathological characteristics and follow-up data were analyzed.

RESULTS: GIST tumors had high expression of SLITRK3 compared with adjacent normal tissues and the expression level gradually increased with risk grade. SLITRK3 protein expression was closely associated with gastrointestinal bleeding, tumor site, tumor size, mitotic index, and National Institutes of Health (NIH) classification. Survival analysis showed that SLITRK3 expression was closely correlated with overall survival and disease-free survival of GIST patients. Multivariate analysis also identified SLITRK3 expression, mitotic index, and NIH stage as significant risk factors of GIST recurrence.

CONCLUSION: SLITRK3 expression is a highly significant predictor of GIST recurrence and metastasis. Combinations of SLITRK3 and NIH stage have strong predictive and prognostic value, and are feasible markers for clinical practice in gastrointestinal stromal tumor.

Keywords: SLITRK3, Gastrointestinal stromal tumor, Biomarkers, Non-epithelial tumors, Risk stratification

Core tip: Prognostic biomarkers are required to refine risk stratification treatment strategies for gastrointestinal stromal tumor (GIST). In this study, we hypothesized that SLIT and NTRK-like family member 3 (SLITRK3) could be used as a prognostic molecular biomarker for GIST. The results indicated that SLITRK3 expression is a highly significant predictor of GIST recurrence and metastasis. Combinations of SLITRK3 and NIH stage have strong predictive and prognostic value, and are feasible markers for clinical practice in gastrointestinal stromal tumor.