Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception
Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein recep...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1074277/full |
| _version_ | 1811186857844670464 |
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| author | Amparo Roa-Colomo Amparo Roa-Colomo María Ángeles López Garrido Pilar Molina-Vallejo Angela Rojas Angela Rojas Mercedes González Sanchez Violeta Aranda-García Javier Salmeron Manuel Romero-Gomez Manuel Romero-Gomez Jordi Muntane Jordi Muntane Jordi Muntane Javier Padillo Jose María Alamo Jose A. Lorente Jose A. Lorente María José Serrano María José Serrano María José Serrano M. Carmen Garrido-Navas |
| author_facet | Amparo Roa-Colomo Amparo Roa-Colomo María Ángeles López Garrido Pilar Molina-Vallejo Angela Rojas Angela Rojas Mercedes González Sanchez Violeta Aranda-García Javier Salmeron Manuel Romero-Gomez Manuel Romero-Gomez Jordi Muntane Jordi Muntane Jordi Muntane Javier Padillo Jose María Alamo Jose A. Lorente Jose A. Lorente María José Serrano María José Serrano María José Serrano M. Carmen Garrido-Navas |
| author_sort | Amparo Roa-Colomo |
| collection | DOAJ |
| description | Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC).Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy.Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression.Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients. |
| first_indexed | 2024-04-11T13:52:18Z |
| format | Article |
| id | doaj.art-043c372ca2ca41c8a7aa4da2f4d7cc88 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-11T13:52:18Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-043c372ca2ca41c8a7aa4da2f4d7cc882022-12-22T04:20:28ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-11-01910.3389/fmolb.2022.10742771074277Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interceptionAmparo Roa-Colomo0Amparo Roa-Colomo1María Ángeles López Garrido2Pilar Molina-Vallejo3Angela Rojas4Angela Rojas5Mercedes González Sanchez6Violeta Aranda-García7Javier Salmeron8Manuel Romero-Gomez9Manuel Romero-Gomez10Jordi Muntane11Jordi Muntane12Jordi Muntane13Javier Padillo14Jose María Alamo15Jose A. Lorente16Jose A. Lorente17María José Serrano18María José Serrano19María José Serrano20M. Carmen Garrido-Navas21Clinical Medicine and Public Health Doctoral Program, University of Granada, Granada, SpainGastroenterology and Hepatology Department, San Cecilio University Hospital, Granada, SpainGastroenterology and Hepatology Department, Virgen De Las Nieves University Hospital, Granada, SpainGenyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, SpainSeliver Group, Institute of Biomedicine of Seville (IBiS)/ Hospital Universitario Virgen Del Rocío/CSIC/Universidad De Sevilla, Seville, SpainSpanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, SpainGastroenterology and Hepatology Department, Virgen De Las Nieves University Hospital, Granada, SpainStatistician at Fundación para la Investigación Biosanitaria Andalucía Oriental Alejandro Otero (FIBAO), Hospital Virgen de las Nieves, Granada, SpainGastroenterology and Hepatology Department, San Cecilio University Hospital, Granada, SpainSeliver Group, Institute of Biomedicine of Seville (IBiS)/ Hospital Universitario Virgen Del Rocío/CSIC/Universidad De Sevilla, Seville, SpainSpanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, SpainSpanish Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute (ISCIII), Madrid, SpainInstitute of Biomedicine of Seville (IBiS), Hospital University Virgen del Rocío/CSIC/University of Seville, Seville, SpainDepartment of Medical Physiology and Biophysics, University of Seville, Seville, Spain0General and Gastrointestinal Surgery Division, Virgen del Rocío University Hospital, Sevilla, Spain0General and Gastrointestinal Surgery Division, Virgen del Rocío University Hospital, Sevilla, SpainGenyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain1Legal Medicine Department, Medicine School, University of Granada, Granada, SpainGenyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, Spain2Comprehensive Oncology Division, Clinical University Hospital, Virgen de las Nieves-IBS, Granada, Spain3Department of Pathological Anatomy, Faculty of Medicine, University of Granada, Granada, SpainGenyo-Centro Pfizer-Universidad De Granada-Junta De Andalucía De Genómica e Investigación Oncológica, Granada, SpainPurpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC).Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy.Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression.Conclusion: Identification and characterization of CECs by ASGR1 and/or miR-122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.https://www.frontiersin.org/articles/10.3389/fmolb.2022.1074277/fullhepatocellular carcinomaliver cirrhosiscirculating tumor cellsprecision medicinecancer interception |
| spellingShingle | Amparo Roa-Colomo Amparo Roa-Colomo María Ángeles López Garrido Pilar Molina-Vallejo Angela Rojas Angela Rojas Mercedes González Sanchez Violeta Aranda-García Javier Salmeron Manuel Romero-Gomez Manuel Romero-Gomez Jordi Muntane Jordi Muntane Jordi Muntane Javier Padillo Jose María Alamo Jose A. Lorente Jose A. Lorente María José Serrano María José Serrano María José Serrano M. Carmen Garrido-Navas Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception Frontiers in Molecular Biosciences hepatocellular carcinoma liver cirrhosis circulating tumor cells precision medicine cancer interception |
| title | Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception |
| title_full | Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception |
| title_fullStr | Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception |
| title_full_unstemmed | Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception |
| title_short | Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception |
| title_sort | hepatocellular carcinoma risk stratification based on asgr1 in circulating epithelial cells for cancer interception |
| topic | hepatocellular carcinoma liver cirrhosis circulating tumor cells precision medicine cancer interception |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1074277/full |
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