Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2020; 26(43): 6853-6866
Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6853
Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage II/III colorectal cancer: Cancer progression and prognosis
Xue-Ling Kang, Li-Rui He, Yao-Li Chen, Shu-Bin Wang
Xue-Ling Kang, Department of Oncology, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong Province, China
Li-Rui He, Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
Yao-Li Chen, Department of Pathology, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
Shu-Bin Wang, Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, China Cancer Institute of Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong Province, China
Author contributions: Kang XL was responsible for the statistical analysis and preparation of manuscript; He LR provided information of the surgical patients; Chen YL provided the patient's pathological and immunohistochemical staining sections; Wang SB is the guarantor of this work and as such, has full access to all the data in the study and takes responsibility for the integrity of the data.
Supported by Sanming Project of Shenzhen, No. SZSM201612041; Shenzhen Science and Technology Innovation Commission Project, No. GJHZ20180420180754917 and No. ZDSYS20190902092855097; and Postdoctoral Science Foundation of China, No. 2018M633095.
Institutional review board statement: The study was reviewed and approved by the Peking University Shenzhen Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: Dataset available from the corresponding author at shubinwang2013@163.com. Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Shu-Bin Wang, MD, PhD, Chief Doctor, Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, China Cancer Institute of Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, No. 1120 Lianhua Road, Futian District, Shenzhen 518036, Guangdong Province, China. shubinwang2013@163.com
Received: June 19, 2020
Peer-review started: June 19, 2020
First decision: September 12, 2020
Revised: September 29, 2020
Accepted: October 19, 2020
Article in press: October 19, 2020
Published online: November 21, 2020
Processing time: 153 Days and 14.2 Hours
Abstract
BACKGROUND

Cancer stem cells (CSCs) are a subpopulation of cancer cells with the potential of self-renewal and differentiation. CSCs play critical roles in tumorigenesis, recurrence, metastasis, radiation tolerance and chemoresistance.

AIM

To assess the expression patterns and clinical potential of doublecortin-like kinase 1 (DCLK1) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), as prognostic CSC markers of colorectal cancer (CRC).

METHODS

The expression of DCLK1 and Lgr5 in CRC tissue sections from 92 patients was determined by immunohistochemistry. Each case was evaluated using a combined scoring method based on signal intensity staining (scored 0-3) and the proportion of positively stained cancer cells (scored 0-3). The final staining score was calculated as the intensity score multiplied by the proportion score. Low expression of DCLK1 and Lgr5 was defined as a score of 0-3; high expression of DCLK1 and Lgr5 was defined as a score of ≥ 4. Specimens were categorized as either high or low expression, and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated.

RESULTS

DCLK1 and Lgr5 expression levels were significantly positively correlated. CRC patients with high DCLK1, Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival. Moreover, high expression of DCLK1 was an independent prognostic factor for recurrence and overall survival in patients with CRC by multivariate analysis (P = 0.026 and P = 0.049, respectively).

CONCLUSION

DCLK1 may be a potential CSC marker for the recurrence and survival of CRC patients.

Keywords: Colorectal cancer; Cancer stem cells; Doublecortin-like kinase 1; Leucine-rich repeat-containing G-protein-coupled receptor 5; Cancer prognosis; Cancer progression

Core Tip: The role of doublecortin-like kinase 1 (DCLK1) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) in patients with stage II/III colorectal cancer (CRC) remains uncertain. In this study, we found a positive correlation between the expression of DCLK1 and Lgr5, suggesting that DCLK1 and Lgr5 were involved in the malignant pathological development of CRC. High DCLK1 expression could predict the risk of recurrence and survival in CRC patients after surgery, which may be used as a potential cancer stem cells marker for the recurrence and survival of stage II/III CRC patients.