Date
2024-09-16
Abstract
Background and Aims Colorectal cancer (CRC) is the second most deadly cancer globally. The rapidly rising incidence rate of CRC, coupled with increased diagnoses in individuals <50 years, indicates that early detection of CRC, and those at an increased risk of CRC development, is paramount to improve the survival rates of these patients. Here, we profile caspase-4 expression across 2 distinct CRC development pathways, sporadic CRC (sCRC) and inflammatory bowel disease-associated CRC (IBD-CRC), to examine its utility as a novel biomarker for CRC risk and diagnosis. Methods Tissue samples from patients with CRC, colonic polyps, IBD-CRC, and sCRC were assessed by immunohistochemistry for caspase-4 expression in epithelial and stromal compartments. RNAseq expression data for caspase-4 in CRC and normal tissue samples were mined from online databases. Results Epithelial caspase-4 expression is selectively elevated in CRC tumor tissue compared to adjacent normal tissue, where it is not expressed. In the sCRC pathway, caspase-4 is expressed in the epithelial and stromal tissue of all histological subtypes of colonic polyps, with a significant increase in epithelial expression from low-grade dysplasia to high-grade dysplasia progression. For the IBD-CRC pathway, caspase-4 epithelial expression was specifically upregulated in dysplastic and neoplastic tissue of IBD-CRC but was not expressed in normal or inflamed tissue. Conclusion This study demonstrates that epithelial caspase-4 is selectively expressed in colon tissue during the development of dysplasia. As such, epithelial caspase-4 represents a promising novel tissue biomarker for CRC risk and diagnosis.
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Description
Publisher
Elsevier
Citation
Gastro Hep Advances, 4 (2), 1000552
Collections
Biological Sciences
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Keywords
colorectal cancer, caspase-4, inflammatory bowel disease, colonic polyp, biomarker
ULRR Identifiers
https://researchrepository.ul.ie/handle/10344/31442
 https://doi.org/10.34961/18955
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Funding Information
Sustainable Development Goals
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Type
Article
Rights
http://creativecommons.org/licenses/by-nc-sa/4.0/
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