Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2015; 21(31): 9348-9357
Published online Aug 21, 2015. doi: 10.3748/wjg.v21.i31.9348
Linc00675 is a novel marker of short survival and recurrence in patients with pancreatic ductal adenocarcinoma
Dou-Dou Li, Zhi-Qiang Fu, Qing Lin, Yu Zhou, Quan-Bo Zhou, Zhi-Hua Li, Lang-Ping Tan, Ru-Fu Chen, Yi-Min Liu
Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Zhi-Qiang Fu, Qing Lin, Yu Zhou, Quan-Bo Zhou, Lang-Ping Tan, Ru-Fu Chen, Department of Pancreaticobiliary and Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, 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: Li DD and Fu ZQ contributed equally to this study; Li DD and Fu ZQ performed the majority of experiments; Lin Q conducted part of the experiments, and contributed to the revision of this paper; Zhou Y and Zhou QB conceived the experiments, analyzed and interpreted the data, and wrote the manuscript; Li ZH and Tan LP participated in the experiments and helped to analyze the data; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Sun Yat-sen Memorial Hospital.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors disclose no conflicts.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author at liuyimin_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. Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan-Jiang Xi Road, Guangzhou 510120, Guangdong Province, China. liuyimin_sysu@163.com
Telephone: +86-20-81332480 Fax: +86-20-81332480
Received: January 28, 2015
Peer-review started: January 29, 2015
First decision: March 10, 2015
Revised: April 7, 2015
Accepted: June 16, 2015
Article in press: June 16, 2015
Published online: August 21, 2015
Processing time: 204 Days and 1 Hours
Abstract

AIM: To detect linc00675 expression in pancreatic ductal adenocarcinoma (PDAC), to analyze the relationship between the expression level of linc00675 and the clinical pathological characteristics, to explore the biological functions of linc00675, and to determine whether linc00675 has independent prognostic value in PDAC.

METHODS: We studied linc00675 expression among eight histologically confirmed PDAC tissue samples and four chronic pancreatitis tissue samples through microarray screening. RT-qPCR was conducted to further investigate linc00675 expression in PDAC cell lines as well as archived tissues from a large cohort of PDAC patients. The correlations between the level of lnc00675 and clinicopathological characteristics and survival in patients with pancreatic cancer were evaluated using Correlation analysis. Univariate and multivariate analyses were conducted to predict whether lnc00675 expression is an independent prognostic and recurrence factor in patients with pancreatic cancer. After downregulating the expression of linc00675 through siRNA, MTT assay, flow cytometry, transwell assay and Western blot were used to explore the biological function of linc00675 in proliferation, invasion, and cell cycle progression of pancreatic cancer cells. The relative molecular expression levels of epithelial-mesenchymal transition were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.

RESULTS: The expression of Linc00675 in PDAC tissue samples was shown to be 672 times that in chronic pancreatitis tissue samples by microarray screening (P = 3.69 × 10-5). This finding was confirmed in tumor tissues from 90 patients with PDAC compared with adjacent normal tissue samples by quantitative RT-PCR. We found that linc00675 overexpression positively correlated with lymph node metastasis (P = 0.005), perineural invasion (P = 0.006), and poor survival (P < 0.001). Univariate and multivariate analyses showed that linc00675 expression served as an independent predictor of overall survival (P = 0.009). Additionally, receiver operating characteristic curve analysis showed that high linc00675 might serve as a predictor of tumor progression within 6 mo to a year after surgery. In vitro functional analysis demonstrated that knockdown of linc00675 attenuated pancreatic cancer cell proliferation and invasion as well as induced S phase arrest. Suppression of linc00675 in pancreatic cancer cells resulted can reverse the progress of epithelial-mesenchymal transition.

CONCLUSION: Linc00675 may function as an oncogene during PDAC development, and its expression is an independent predictor of unfavorable prognosis in patients with PDAC.

Keywords: Linc00675; Long noncoding RNAs; Prognosis biomarker; Pancreatic cancer; Epithelial-mesenchymal transition

Core tip: This is the first study to report that linc00675 is more highly expressed in pancreatic ductal adenocarcinoma (PDAC) tissues than in adjacent normal tissues. Overexpression of linc00675 in PDAC tissues positively correlated with short survival and tumor progression. The prominent finding in this study is that linc00675 is an independent prognostic marker for predicting the survival of PDAC patients after surgery.