Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2020; 26(26): 3814-3833
Published online Jul 14, 2020. doi: 10.3748/wjg.v26.i26.3814
Expression of Notch pathway components (Numb, Itch, and Siah-1) in colorectal tumors: A clinicopathological study
Sinem Cil Gonulcu, Betul Unal, Ibrahim Cumhur Bassorgun, Mualla Ozcan, Hasan Senol Coskun, Gulsum Ozlem Elpek
Sinem Cil Gonulcu, Betul Unal, Ibrahim Cumhur Bassorgun, Mualla Ozcan, Gulsum Ozlem Elpek, Department of Pathology, Akdeniz University, School of Medicine, Antalya 07070, Turkey
Hasan Senol Coskun, Department of Oncology, Akdeniz University, School of Medicine, Antalya 07070, Turkey
Author contributions: Gonulcu SC was involved in the conceptualization, data curation, funding acquisition, investigation, writing-original draft; Unal B took part in the resources, investigation, and writing review and editing; Bassorgun IC contributed to the investigation, visualization, and writing review and editing; Ozcan M was involved in the data curation, investigation and resources; Coskun HS provided clinical data and resources; Elpek GO performed the conceptualization, data curation, funding acquisition, investigation, methodology, project administration, supervision, visualization, writing review, and editing; all authors have read and approved the final manuscript.
Supported by Akdeniz University Scientific Research Foundation, Turkey, No. 2017040103020.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
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: Gulsum Ozlem Elpek, MD, Professor, Department of Pathology, Akdeniz University, School of Medicine, Dumlupınar Bulvarı, Antalya 07070, Turkey. elpek@akdeniz.edu.tr
Received: February 26, 2020
Peer-review started: February 26, 2020
First decision: March 18, 2020
Revised: May 18, 2020
Accepted: June 25, 2020
Article in press: June 25, 2020
Published online: July 14, 2020
Abstract
BACKGROUND

The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs, including the colon. Accordingly, studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression. Although Numb, Itch, and seven in absentia homolog-1 (Siah-1) have been shown to contribute to the regulation of Notch signaling, their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.

AIM

To evaluate Numb, Itch, and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.

METHODS

Expression of Notch-1, Numb, Itch, and Siah-1 was investigated in 50 colorectal carcinomas, 30 adenomas, and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analyses.

RESULTS

In contrast to Notch-1, which is expressed at higher levels in tumor tissues and adenomas, expression of Numb, Itch, and Siah-1 was stronger and more frequent in normal mucosa (P < 0.01). There was a positive correlation between Notch-1 expression and high histological grade, the presence of lymph node metastasis, and advanced-stage tumors, whereas expression of Numb, Itch, and Siah-1 was absent or reduced in tumors with these clinicopathological parameters (P < 0.05). In survival analysis, expression of Notch was related to poor prognosis but that of Numb, Itch, and Siah-1 correlated with improved survival (P < 0.05). Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis (P < 0.05).

CONCLUSION

Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma (CRC) progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.

Keywords: Colorectal adenomas, Colorectal cancer, Notch-1, Numb, Itch, Siah-1

Core tip: This report describes a preliminary study to investigate Numb, Itch, and Siah-1 expression in colorectal tumors and to evaluate their relationship with Notch-1 expression and their roles in oncogenesis and prognosis. Our findings confirm the role of Notch-1 in colorectal carcinoma (CRC) and emphasize that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also indicate that Numb, Itch, and Siah-1 might be involved in the Notch-1 signaling pathway during CRC progression. Accordingly, these three proteins might be key in possible therapies targeting Notch-1 to treat colorectal carcinoma.