Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2017; 23(31): 5787-5797
Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5787
Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer
Yuan Xie, Jian-Zhen Lin, An-Qiang Wang, Wei-Yu Xu, Jun-Yu Long, Yu-Feng Luo, Jie Shi, Zhi-Yong Liang, Xin-Ting Sang, Hai-Tao Zhao
Yuan Xie, Jian-Zhen Lin, An-Qiang Wang, Wei-Yu Xu, Jun-Yu Long, Xin-Ting Sang, Hai-Tao Zhao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Yu-Feng Luo, Jie Shi, Zhi-Yong Liang, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Author contributions: Xie Y designed the research, collected the clinical data and wrote the manuscript; Lin JZ and Shi J helped to analyze the data; Wang AQ, Xu WY and Long JY followed the patients; Luo YF helped to perform the experiments; Liang ZY provided paraffin-embedded tissues for the experiments; Sang XT and Zhao HT provided financial support for this work; Shi J, Liang ZY, Sang XT and Zhao HT are co-corresponding authors, and they contributed equally to this work; all authors read and approved the final manuscript.
Supported by International Science and Technology Cooperation Projects, No. 2015DFA30650 and No. 2016YFE0107100; The Capital Special Research Project for Clinical Application, No. Z151100004015170; Capital Special Research Project for Health Development, No. 2014-2-4012; and Beijing Nature Science Foundation for Young Scholars, No. 7164293.
Institutional review board statement: The publication of this manuscript has been reviewed and approved by the PUMCH Institutional Review Board.
Informed consent statement: All patients or their families signed informed consent statements before surgery, and surgical procedures were performed according to the approved guidelines.
Conflict-of-interest statement: We declare that the authors have no conflict of interest.
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: Hai-Tao Zhao, MD, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. zhaoht@pumch.cn
Telephone: +86-10-69156042 Fax: +86-10-69156042
Received: May 30, 2017
Peer-review started: May 31, 2017
First decision: June 22, 2017
Revised: July 3, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: August 21, 2017
Processing time: 81 Days and 9.3 Hours
Abstract
AIM

To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis.

METHODS

A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-score values. The correlations between TTK expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression.

RESULTS

In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues (P < 0.001 and P = 0.026, respectively). Using the median H-score as the cutoff value, it was discovered that, GBC patients with higher levels of TTK expression in the nucleus, but not the cytoplasm, had favorable overall survival (P < 0.001), and it was still statistically meaningful in Cox regression analysis. Further investigation indicated that there were close negative correlations between TTK expression and tumor differentiation (P = 0.041), CA 19-9 levels (P = 0.016), T stage (P < 0.001), nodal involvement (P < 0.001), distant metastasis (P = 0.024) and TNM stage (P < 0.001).

CONCLUSION

The expression of TTK in GBC is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC.

Keywords: Threonine and tyrosine kinase, Biomarker, Prognosis, Gallbladder cancer

Core tip: Numerous studies demonstrate that high levels of threonine and tyrosine kinase (TTK) are present in many types of human malignancies, and its overexpression closely correlates with early recurrence and poor survival. However, no prior studies have attempted to concentrate on the expression of TTK in patients with gallbladder cancer (GBC). In this study, we detected the expression of TTK in GBC specimens and analyzed the associations between TTK expression and clinicopathological parameters and clinical prognosis.