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CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype
The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including wors...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378918/ https://www.ncbi.nlm.nih.gov/pubmed/32742454 http://dx.doi.org/10.7150/jca.44697 |
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author | Zhuo, Jian-Yong Lu, Di Tan, Win-Yen Zheng, Shu-Sen Shen, You-Qing Xu, Xiao |
author_facet | Zhuo, Jian-Yong Lu, Di Tan, Win-Yen Zheng, Shu-Sen Shen, You-Qing Xu, Xiao |
author_sort | Zhuo, Jian-Yong |
collection | PubMed |
description | The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including worse overall survival and early tumor recurrence after hepatectomy and liver transplantation. CK19-positive HCCs are resistant to chemotherapies as well as local treatment. This subset of HCC is thought to derive from liver progenitor cells and can be induced by extracellular stimulation such as hypoxia. Besides being a stemness marker, CK19 plays an important role in promoting malignant property of HCC. The regulatory network associated with CK19 expression has been summarized that extracellular stimulations which transmit into cytoplasm through signal transduction pathways (TGF-β, MAKP/JNK and MEK-ERK1/2), further induce important nuclear transcriptional factors (SALL4, AP1, SP1) to activate CK19 promoter. Novel noncoding RNAs are also involved in the regulation of CK19 expression. TGFβR1 becomes a therapeutic target for CK19-positive HCC. In conclusion, CK19 can be a potential biomarker for predicting poor prognosis after surgical and adjuvant therapies. CK19-pisitive HCCs exhibit distinctive molecular profiling, should be diagnosed and treated as a separate subtype of HCCs. |
format | Online Article Text |
id | pubmed-7378918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-73789182020-07-30 CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype Zhuo, Jian-Yong Lu, Di Tan, Win-Yen Zheng, Shu-Sen Shen, You-Qing Xu, Xiao J Cancer Review The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including worse overall survival and early tumor recurrence after hepatectomy and liver transplantation. CK19-positive HCCs are resistant to chemotherapies as well as local treatment. This subset of HCC is thought to derive from liver progenitor cells and can be induced by extracellular stimulation such as hypoxia. Besides being a stemness marker, CK19 plays an important role in promoting malignant property of HCC. The regulatory network associated with CK19 expression has been summarized that extracellular stimulations which transmit into cytoplasm through signal transduction pathways (TGF-β, MAKP/JNK and MEK-ERK1/2), further induce important nuclear transcriptional factors (SALL4, AP1, SP1) to activate CK19 promoter. Novel noncoding RNAs are also involved in the regulation of CK19 expression. TGFβR1 becomes a therapeutic target for CK19-positive HCC. In conclusion, CK19 can be a potential biomarker for predicting poor prognosis after surgical and adjuvant therapies. CK19-pisitive HCCs exhibit distinctive molecular profiling, should be diagnosed and treated as a separate subtype of HCCs. Ivyspring International Publisher 2020-06-28 /pmc/articles/PMC7378918/ /pubmed/32742454 http://dx.doi.org/10.7150/jca.44697 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Review Zhuo, Jian-Yong Lu, Di Tan, Win-Yen Zheng, Shu-Sen Shen, You-Qing Xu, Xiao CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title | CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title_full | CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title_fullStr | CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title_full_unstemmed | CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title_short | CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype |
title_sort | ck19-positive hepatocellular carcinoma is a characteristic subtype |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378918/ https://www.ncbi.nlm.nih.gov/pubmed/32742454 http://dx.doi.org/10.7150/jca.44697 |
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