Caspase-4 has potential utility as a colorectal tissue biomarker for dysplasia and early-stage cancer

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 im...

Full description

Bibliographic Details
Authors: Kane, Laura E., Flood, Brian, Manils Pacheco, Joan, McSkeane, Donna E., Smith, Aoife P., Tosetto, Miriam, Alalawi, Fatema, Fay, Joanna, Kay, Elaine W., Dunne, Cara, McQuaid, Stephen, Loughrey, Maurice B., O’Sullivan, Jacintha, Ryan, Elizabeth J., Sheahan, Kieran, Doherty, Glen A., Creagh, Emma M.
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/217719
Online Access:https://hdl.handle.net/2445/217719
Access Level:Open access
Keyword:Pòlips (Patologia)
Marcadors bioquímics
Inflamació
Càncer colorectal
Polyps (Pathology)
Biochemical markers
Inflammation
Colorectal cancer
Description
Summary: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 two 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-associated CRC, and sporadic CRC were assessed by Immunohistochemistry (IHC) 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 tumour 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 LGD to HGD progression. For the IBDCRC 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. Conclusions: 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. 

Similar Items