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Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis

Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant...

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Autores principales: Dastych, Milan, Hubatka, Frantisek, Turanek-Knotigova, Pavlina, Masek, Josef, Kroupa, Radek, Raška, Milan, Turanek, Jaroslav, Prochazka, Lubomir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262190/
https://www.ncbi.nlm.nih.gov/pubmed/34257584
http://dx.doi.org/10.3389/pore.2021.614281
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author Dastych, Milan
Hubatka, Frantisek
Turanek-Knotigova, Pavlina
Masek, Josef
Kroupa, Radek
Raška, Milan
Turanek, Jaroslav
Prochazka, Lubomir
author_facet Dastych, Milan
Hubatka, Frantisek
Turanek-Knotigova, Pavlina
Masek, Josef
Kroupa, Radek
Raška, Milan
Turanek, Jaroslav
Prochazka, Lubomir
author_sort Dastych, Milan
collection PubMed
description Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.
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spelling pubmed-82621902021-07-12 Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis Dastych, Milan Hubatka, Frantisek Turanek-Knotigova, Pavlina Masek, Josef Kroupa, Radek Raška, Milan Turanek, Jaroslav Prochazka, Lubomir Pathol Oncol Res Society Journal Archive Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon. Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses. Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner. Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique. Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma. Frontiers Media S.A. 2021-03-30 /pmc/articles/PMC8262190/ /pubmed/34257584 http://dx.doi.org/10.3389/pore.2021.614281 Text en Copyright © 2021 Dastych, Hubatka, Turanek-Knotigova, Masek, Kroupa, Raška, Turanek and Prochazka. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Society Journal Archive
Dastych, Milan
Hubatka, Frantisek
Turanek-Knotigova, Pavlina
Masek, Josef
Kroupa, Radek
Raška, Milan
Turanek, Jaroslav
Prochazka, Lubomir
Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title_full Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title_fullStr Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title_full_unstemmed Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title_short Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
title_sort overexpression of cd44v8-10 in colon polyps—a possible key to early diagnosis
topic Society Journal Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262190/
https://www.ncbi.nlm.nih.gov/pubmed/34257584
http://dx.doi.org/10.3389/pore.2021.614281
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