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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Comparative study of ROR2 and WNT5a expression in squamous/adenosquamous carcinoma and adenocarcinoma of the gallbladder
Zheng-Chun Wu, Li Xiong, Ling-Xiang Wang, Xiong-Ying Miao, Zi-Ru Liu, Dai-Qiang Li, Qiong Zou, Kui-Jie Liu, Hua Zhao, Zhu-Lin Yang
Zheng-Chun Wu, Li Xiong, Ling-Xiang Wang, Xiong-Ying Miao, Zi-Ru Liu, Kui-Jie Liu, Hua Zhao, Zhu-Lin Yang, General Surgery Department, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Zheng-Chun Wu, Li Xiong, Ling-Xiang Wang, Xiong-Ying Miao, Zi-Ru Liu, Kui-Jie Liu, Hua Zhao, Zhu-Lin Yang, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Dai-Qiang Li, Department of Pathology, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Qiong Zou, Department of Pathology, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China
Author contributions: Wu ZC, Xiong L and Wang LX carried out studies and wrote the paper; Yang ZL designed the study and revised the paper; Liu ZR, Liu KJ and Yang ZL performed the statistical analysis; Miao XY and Zhao H conceived of the study and participated in the design and coordination; Li DQ and Zou Q collected specimens and experimental materials; Wu ZC and Xiong L contributed equally to this work.
Supported by the National Natural Science Foundation of China, No. 81372628 and No. 81402536; the Changsha Science and Technology Plan, No. K1205018-31.
Institutional review board statement: This study was approved by the Institutional Review Board of Second Xiangya Hospital, Central South University.
Clinical trial registration statement: This registration policy applies to prospective, randomized, controlled trials only.
Informed consent statement: This study is exempt from informed consent since it is a retrospective study and the data collection and analysis were carried out without disclosing patients’ identities.
Conflict-of-interest statement: All authors declare that there are no commercial, personal or any other potential conflicting interests related to the submitted manuscript.
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: Dr. Zhu-Lin Yang, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, 139 Middle Renmin Rd., Changsha 410011, Hunan Province, China. 4896142@qq.com
Telephone: +86-731-88187376 Fax: +86-731-84898168
Received: November 29, 2016
Peer-review started: November 30, 2016
First decision: December 28, 2016
Revised: February 1, 2017
Accepted: March 2, 2017
Article in press: March 2, 2017
Published online: April 14, 2017
AIM
To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC).
METHODS
EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients.
RESULTS
Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors.
CONCLUSION
SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.
Core tip: Gallbladder carcinoma (GBC) is a highly aggressive malignancy of the biliary tract. However, biological markers for the diagnosis, prognosis, and targeted therapy of GBCs are still not clear. In this study, we investigated the clinicopathological significance of ROR2 and WNT5a in squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC) of the gallbladder. We found that positive ROR2 or WNT5a expression in both SC/ASC or AC patients were negatively correlated with postoperative survival rate and positively correlated with mortality. Elevated expression levels of ROR2 or WNT5a are associated with a higher risk of GBC and are independent prognostic predictors.
