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Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features
Alpha-1 antitrypsin deficiency (A1ATD) is underdiagnosed and associated with liver diseases. Here, we genotyped 130 patients with biliary tract cancer (BTC) scheduled for liver resection and found A1ATD in 10.8% of the patients. A1ATD was found in all BTC subtypes, and patients had similar clinical...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297722/ https://www.ncbi.nlm.nih.gov/pubmed/37371133 http://dx.doi.org/10.3390/cells12121663 |
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author | Cornillet, Martin Zemack, Helen Jansson, Hannes Sparrelid, Ernesto Ellis, Ewa Björkström, Niklas K. |
author_facet | Cornillet, Martin Zemack, Helen Jansson, Hannes Sparrelid, Ernesto Ellis, Ewa Björkström, Niklas K. |
author_sort | Cornillet, Martin |
collection | PubMed |
description | Alpha-1 antitrypsin deficiency (A1ATD) is underdiagnosed and associated with liver diseases. Here, we genotyped 130 patients with biliary tract cancer (BTC) scheduled for liver resection and found A1ATD in 10.8% of the patients. A1ATD was found in all BTC subtypes, and patients had similar clinical features as non-A1ATD BTC, not permitting their identification using clinical routine liver tests. In intrahepatic cholangiocarcinoma (iCCA), the abundance of A1AT protein was increased in the tumor and appeared to be influenced by the genomic alterations. On the one hand, BTC with A1ATD had lower perineural invasion at histopathology and displayed a longer survival, suggesting that a deficiency in this protein is associated with a less aggressive phenotype. On the other hand, iCCA with high A1AT expression had more advanced tumor staging and enriched pathways for complement system and extracellular matrix interactions, indicating that A1AT protein might contribute to a more aggressive phenotype. With increased awareness, screening, and basic studies, A1ATD could represent one more layer of stratification for future targeted therapies in BTC. |
format | Online Article Text |
id | pubmed-10297722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102977222023-06-28 Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features Cornillet, Martin Zemack, Helen Jansson, Hannes Sparrelid, Ernesto Ellis, Ewa Björkström, Niklas K. Cells Communication Alpha-1 antitrypsin deficiency (A1ATD) is underdiagnosed and associated with liver diseases. Here, we genotyped 130 patients with biliary tract cancer (BTC) scheduled for liver resection and found A1ATD in 10.8% of the patients. A1ATD was found in all BTC subtypes, and patients had similar clinical features as non-A1ATD BTC, not permitting their identification using clinical routine liver tests. In intrahepatic cholangiocarcinoma (iCCA), the abundance of A1AT protein was increased in the tumor and appeared to be influenced by the genomic alterations. On the one hand, BTC with A1ATD had lower perineural invasion at histopathology and displayed a longer survival, suggesting that a deficiency in this protein is associated with a less aggressive phenotype. On the other hand, iCCA with high A1AT expression had more advanced tumor staging and enriched pathways for complement system and extracellular matrix interactions, indicating that A1AT protein might contribute to a more aggressive phenotype. With increased awareness, screening, and basic studies, A1ATD could represent one more layer of stratification for future targeted therapies in BTC. MDPI 2023-06-19 /pmc/articles/PMC10297722/ /pubmed/37371133 http://dx.doi.org/10.3390/cells12121663 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Cornillet, Martin Zemack, Helen Jansson, Hannes Sparrelid, Ernesto Ellis, Ewa Björkström, Niklas K. Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title | Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title_full | Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title_fullStr | Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title_full_unstemmed | Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title_short | Increased Prevalence of Alpha-1-Antitrypsin Deficiency in Patients with Biliary Tract Cancer and Its Associated Clinicopathological Features |
title_sort | increased prevalence of alpha-1-antitrypsin deficiency in patients with biliary tract cancer and its associated clinicopathological features |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297722/ https://www.ncbi.nlm.nih.gov/pubmed/37371133 http://dx.doi.org/10.3390/cells12121663 |
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