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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Low RASSF6 expression in pancreatic ductal adenocarcinoma is associated with poor survival
Hui-Lin Ye, Dou-Dou Li, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Yi-Min Liu, Rui-Wan Chen, Zhi-Hua Li, Ru-Fu Chen
Hui-Lin Ye, Qing Lin, Yu Zhou, Quan-Bo Zhou, Bing Zeng, Zhi-Qiang Fu, Wen-Chao Gao, Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Rui-Wan Chen, Department of Radiotherapy, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Zhi-Hua Li, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Author contributions: Ye HL and Li DD contributed equally to this study; Ye HL and Lin Q performed the majority of experiments; Li DD conducted part of the experiment and revised the paper; Li ZH and Chen RF conceived the experiments, analyzed and interpreted data and wrote the manuscript; Zhou Y, Zhou QB, Zeng B, Fu ZQ, Gao WC, Liu YM and Chen RW participated in the experiment and helped analyze the data; all authors read and approved the final manuscript.
Ethics approval: The study was reviewed and approved by the Institutional Review Board of Sun Yat-sen Memorial hospital and the Ethics Committee of Sun Yat-sen Memorial Hospital.
Informed consent: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest: The authors disclose no conflicts of interest.
Data sharing: The technical appendix, statistical code, and dataset are available from the corresponding author at chenrf_sysu@163.com. Consent was not obtained but the presented data are anonymized and the risk of identification is low.
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. Ru-Fu Chen, Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yan-Jiang Xi Road, Guangzhou 510120, Guangdong Province, China.
chenrf_sysu@163.com
Telephone: +86-21-81332020 Fax: +86-21-81332020
Received: November 29, 2014
Peer-review started: November 29, 2014
First decision: December 26, 2014
Revised: January 24, 2015
Accepted: February 13, 2015
Article in press: February 13, 2015
Published online: June 7, 2015
Processing time: 193 Days and 22.7 Hours
AIM: To analyze RASSF6 expression in pancreatic ductal adenocarcinoma (PDAC) and to determine whether RASSF6 has an independent prognostic value in PDAC.
METHODS: We studied RASSF6 expression in 96 histologically confirmed PDAC samples and 20 chronic pancreatitis specimens using immunohistochemistry and real-time quantitative reverse transcription-PCR. PDAC issues were then classified as RASSF6 strongly positive, weakly positive or negative. RASSF6 mRNA and protein expression in PDAC samples with strong positive staining was further evaluated using real-time PCR and Western blot analysis. Lastly, correlations between RASSF6 staining and patients’ clinicopathological variables and outcomes were assessed.
RESULTS: RASSF6 was negatively expressed in 51 (53.1%) PDAC samples, weakly positively expressed in 29 (30.2%) and strongly positively expressed in 16 (16.7%), while its expression was much higher in para-tumor tissues and chronic pancreatitis tissues. Positive relationships between RASSF6 expression and T-stage (P = 0.047) and perineural invasion (P = 0.026) were observed. The median survival time of strongly and weakly positive and negative RASSF6 staining groups was 33 mo, 15 mo and 11 mo, respectively. Cox multivariate analysis indicated that RASSF6 was an independent prognostic indicator of overall survival in patients with PDAC. A survival curve analysis revealed that increased RASSF6 expression was correlated with better overall survival (P = 0.009).
CONCLUSION: RASSF6 expression is an independent biomarker of an unfavorable prognosis in patients with PDAC.
Core tip: This is the first study that provides evidence for the prognostic value and potential tumor suppressor activity of RASSF6 in pancreatic ductal adenocarcinoma. The prominent findings in this study are that RASSF6 is an independent prognostic marker for predicting the survival of pancreatic ductal adenocarcinoma patients after curative operations and that the expression of RASSF6 might decrease with the development of cancer.
