Advancing Non-Invasive Colorectal Cancer Screening

Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The Sialyl-Tn (STn) antigen, frequently expressed in pre-malignant lesions and adenocarcinomas, has been shown to be detected by the novel monoclonal antibody L2A5. In this study, we explored the potential of L2A5 as a non-invasive CRC screening method in an attempt to overcome current limitations. The subjects were categorised into four groups based on colonoscopy findings: no lesion (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC). Slot blot analysis using the L2A5 antibody was performed on stool samples from 95 colonoscopy patients. Our findings showed a differential STn expression between the different clinical groups, evidencing excellent discrimination between NL and CRC (AUC, 0.8252; 95% CI: 0.6983-0.9521; sensitivity, 70%). Moreover, moderate discrimination between the NL+LGD and HGD+CRC groups was discerned (AUC, 0.7766; 95% CI: 0.6792-0.8740; sensitivity, 58%). These findings support the application of L2A5 as a tool for detecting STn, allowing for the identification of advanced lesions in non-invasive CRC screening.

Descrição

Funding Information: This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through CI-IPOP project UIDP/00776/2020, FCT project BioFaec (http://doi.org/10.54499/2022.09051.PTDC, accessed on 1 March 2024) and ONCOSCREEN (grant agreement No. 101097036) and the funding UIDP/04378/2020 and UIDB/04378/2020 to UCIBIO research unit and LA/P/0140/2020 to the i4HB Associate Laboratory. P.A.V. also thanks project InnoGlyco (ref: 2022.04607.PTDC). This work was cofounded by the project “The Porto Comprehensive Cancer Centre Raquel Seruca” with the reference NORTE-01-0145-FEDER-0726678—Consorcio PORTO. CCC—Porto.Comprehensive Cancer Centre Raquel Seruca, supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF), Portugal. FCT is co-financed by the European Social Fund (ESF) under the Human Potential Operation Programme (POPH) from the National Strategic Reference Framework (NSRF). The authors also thank the financial support of the Portuguese Oncology Institute of Porto— Research Centre (CI-IPOP-77–2017-2024). The authors also wish to acknowledge funding from FCT for PhD Grants BD/04511/2024 (ME) and UI/BD/154820/2023 (DARS). JS would like to acknowl edge an Advanced Investigation Grant from the Portuguese League Against Cancer. RC would like to acknowledge 2022.09051.PTDC + PI177-CI-IPOP-01-2023-HORIZON-ONCOSCREEN grant under the scopes of BioFaec and ONCOSCREEN. LL acknowledges the research position from FCT (DL 57/2016/CP1491/CT0002) and under the scope of ONCOSCREEN (PI177-CI-IPOP-01-2023- HORIZON-ONCOSCREEN_ASSRES). Publisher Copyright: © 2025 by the authors.

Palavras-chave

Colorectal cancer Early screening L2A5 antibody Precancerous lesions Sialyl-Tn Stool samples Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being