Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2017; 23(1): 110-120
Published online Jan 7, 2017. doi: 10.3748/wjg.v23.i1.110
Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis
Akram Yusup, Bailikezi Huji, Cheng Fang, Fei Wang, Tuerxunjiang Dadihan, Hai-Jiang Wang, Halmurat Upur
Akram Yusup, Bailikezi Huji, Hai-Jiang Wang, Department of Gastrointestinal Surgery and Record Room, Affiliated Tumor Hospital, Xin Jiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China
Cheng Fang, Fei Wang, Department of Gastrointestinal Surgery, Xi Jing Digestive Disease Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Tuerxunjiang Dadihan, Department of Human Anatomy of Preclinical College, Xinjiang Medical University, Urumqi 830011, Xinjiang Uygur Autonomous Region, China
Halmurat Upur, Central Laboratory, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Author contributions: Yusup A, Wang HJ and Upur H conceived and designed the study; Yusup A wrote the first draft of the manuscript; Huji B assisted with the collection of the clinicopathological materials and the overall statistics and analysis of the data; Fang C, Wang F and Dadihan T helped perform experiments such as immunohistochemistry, qRT-PCR and Western blot; all authors read and approved the final manuscript.
Supported by the Natural Science Fund of the Xinjiang Uygur Autonomous Region, No. 2014211C111.
Institutional review board statement: The study design and procedures described below were approved by the Ethics Committee of the Affiliated Tumor Hospital of Xinjiang Medical University (No. W-201401).
Informed consent statement: All patients provided informed written consent prior to their participation.
Conflict-of-interest statement: No conflict of interest exists in the submission of this 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: Halmurat Upur, PhD, Central Laboratory, Xinjiang Medical University, 393 Xinyi Road, Urumqi 830054, Xinjiang Uygur Autonomous Region, China. bilik0731@163.com
Telephone: +86-991-4365765 Fax:+86-991-4365231
Received: August 27, 2016
Peer-review started: August 29, 2016
First decision: September 28, 2016
Revised: October 19, 2016
Accepted: December 2, 2016
Article in press: December 2, 2016
Published online: January 7, 2017
Abstract
AIM

To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival.

METHODS

This study examined the expression of TFF1, TFF3 and TWIST1 in a total of 75 tumor samples, 47 matched normal samples (15 cm from the lesion margin), 30 metastatic lymph nodes, and 10 liver metastatic cancer samples from patients with CRC. The relationship was then analyzed between the protein expression and different clinical records. TFF1, TFF3, TWIST1,E-cadherin, vimentin and β-catenin mRNA and protein expression levels were measured in colon cancer cell lines with different metastatic potentials (HIEC, HT29, SW620, and LoVo cells), and the correlation of the expression levels with epithelial-mesenchymal transition (EMT) was discussed.

RESULTS

It was found that 66.7% (50/75), 78.7% (59/75) and 54.7% (41/75) of tumor tissue samples exhibited positive staining for TFF1, TFF3 and TWIST1 and so did 27.3% (13/47), 100% (47/47) and 17% (8/47) of adjacent normal colorectal tissues. Compared with adjacent normal tissues, significant differences were found in the expression of all three proteins in different cancerous tissues (P < 0.05). Higher expression of TFF3 and TWIST1 was significantly correlated with lymph node metastasis (P = 0.034, P = 0.000), advanced stage (P = 0.031, P = 0.003), and poorer survival (P = 0.042 for the TFF3 group, P = 0.003 for the TWIST1 group). The expression of TFF3 and TWIST1 in cancer cell lines was higher than that in HIEC (a normal human intestinal epithelial cell line)(P < 0.05), and the expression intensity demonstrated a tendency to rise with increased metastatic potential both at the protein and mRNA levels. However, TFF1 expression demonstrated the opposite tendency. It was also observed that the expression of E-cadherin and β-catenin tended to decrease while that of vimentin, TWIST1 and Snail tended to rise with the increase in metastatic potential.

CONCLUSION

The expression of TFF3 and TWIST1 might be associated with the survival of patients with CRC after curative resection and might be pivotal predictors of disease progression. TFF3 may be correlated to the invasiveness of CRC.

Keywords: Colorectal cancer, Trefoil factors, TWIST1, Survival, Metastasis

Core tip: The expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and their roles in metastasis and survival are unclear. This study involved the preliminary examination of the expression of TFF1, TFF3 and TWIST1 in CRC tissues and different metastasis samples from patients and cell lines. This study also analyzed the relationship between the expression of these proteins and metastatic potential and survival. It can be concluded that the expression of TFF3 and TWIST1 in CRC might be associated with patient survival after curative resection and may play an active role in disease progression. Finally, TFF3 may be correlated to the invasiveness of the CRC.