Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer

Sep 21, 2026

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Colorectal cancer (CRC) is a major global health burden with high mortality. This review investigates how APC mutations disrupt β-catenin regulation and link β-catenin dysregulation to epithelial-mesenchymal transition (EMT) and clinical outcomes. Tissue from 96 CRC patients and 40 para-cancerous controls was assessed by immunohistochemistry for β-catenin, E-cadherin, ZEB1, Snail, and vimentin, with genomic DNA analyzed for APC mutations using next-generation sequencing.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Background

Methodology

Results

Conclusion

Introduction

Open Access Original Article DOI: 10.7759/cureus.53104 Review began 01/17/2024 Review ended 01/23/2024 Published 01/28/2024 © Copyright 2024 Hussein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. Aberrant β-Catenin Expression and Its Association With Epithelial-Mesenchymal Transition and Clinical Outcomes of Colorectal Cancer Zihel H. Hussein 1 , Bashar Al Hassawi 1 , Qais Ibraheem 1 1. Department of Anatomy, Biology, and Histology, College of Medicine, University of Duhok, Duhok, IRQ Corresponding author: Qais Ibraheem, [qaisibraheem@uod.ac](qaisibraheem@uod.ac) Abstract Background Colorectal cancer (CRC) is a significant global health challenge with high mortality rates. Dysregulation of β-catenin, epithelial-mesenchymal transition (EMT), and adenomatous polyposis coli (APC) are crucial in CRC development. Mutations in the APC gene lead to aberrant β-catenin expression, a key player in CRC pathogenesis. β-catenin not only influences canonical Wnt signaling but also regulates EMT. This study investigated the correlation between APC mutations, β-catenin dysregulation, and EMT induction in CRC. Methodology Tissue samples from 96 CRC patients and 40 para-cancerous normal tissues were collected and subjected to immunohistochemistry to assess β-catenin, E-cadherin, ZEB1, Snail, and vimentin expression. Genomic DNA was extracted and analyzed for APC mutations. Next-generation sequencing was employed for data analysis. Results Aberrant β-catenin expression was found in 82.3% of CRC cases and correlated with advanced clinicopathological factors. Aberrant β-catenin expression was associated with age (p=0 .01), tumor invasion depth (p=0 .03), nodal/distant metastasis (p=0 .001 and 0 .004), and vascular invasion (p=0 .001) . Aberrant β -catenin was correlated with EMT status. A positive correlation was observed between aberrant β-catenin expression and ZEB1 (p=0 .001), Snail (p=0 .001), vimentin (p=0 .001), and loss of membranous E-cadherin (p=0001) . Coexistence of aberrant β-catenin and EMT markers was associated with advanced CRC progression. Cancerous tissues displayed higher aberrant β-catenin and EMT markers expression than paracancerous tissues. APC mutations were present in 59.3% of cases, with 91 .2% of mutated APC cases showing aberrant β-catenin expression. The coexistence of APC mutation and aberrant β-catenin expression was correlated with the clinical outcomes of CRC patients. Mutated APC cases exhibited significantly increased EMT marker expression. Conclusion This study underscores the importance of aberrant β-catenin expression in CRC progression, linked to APC mutations and EMT induction. Understanding these relationships could aid in developing targeted therapies for CRC. Categories: Gastroenterology, Genetics, Pathology Keywords: mutation, apc, epithelial mesenchymal transition, β-catenin, colorectal cancer Introduction Colorectal cancer (CRC) remains a formidable global health challenge, accounting for a significant number of cancer-related deaths worldwide. Understanding the intricate molecular mechanisms governing CRC development is crucial to advance early diagnosis, treatment, and prevention strategies. Among the key molecular players that drive colorectal tumorigenesis dysregulation of β-catenin signaling, epithelialmesenchymal transition (EMT) and adenomatous polyposis coli (APC), have emerged as focal points of research due to their pivotal roles in this malignancy [1] . β-catenin, a multifunctional protein encoded by the CTNNB1 gene, plays a central role in a multitude of cellular processes. One of its primary functions is its participation in the canonical Wnt signaling pathway, where it acts as a key regulator. In the absence ofWnt ligands, a destruction c

FAQs

What biological process connects APC mutations, β-catenin dysregulation, and EMT in colorectal cancer?

APC mutations disrupt the β-catenin destruction complex, allowing β-catenin accumulation and nuclear signaling. β-catenin then regulates EMT programs, contributing to tumor progression and clinical changes.

How were β-catenin and EMT markers measured in this study?

The study used immunohistochemistry on tissue samples to assess β-catenin, E-cadherin, ZEB1, Snail, and vimentin expression.

What clinical associations were observed with aberrant β-catenin expression?

Aberrant β-catenin was associated with advanced clinicopathological factors, including patient age, tumor invasion depth, nodal or distant metastasis, vascular invasion, and EMT status.

Sep 21, 2026

Uploaded by Patrick