Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma

The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis. ALK status was investigated using immunohistochemistry (IHC), reverse transcription-quantitativ...

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Main Authors:	LIU, JIANHUA, JIN, HAOSHENG, TIAN, HONGXIA, LIAN, GUODA, CHEN, SHAOJIE, LI, JIAYU, ZHANG, XUCHAO, MA, DONG
Format:	Online
Language:	English
Published:	D.A. Spandidos 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727030/

id	pubmed-4727030
recordtype	oai_dc
spelling	pubmed-47270302016-02-11 Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma LIU, JIANHUA JIN, HAOSHENG TIAN, HONGXIA LIAN, GUODA CHEN, SHAOJIE LI, JIAYU ZHANG, XUCHAO MA, DONG Articles The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis. ALK status was investigated using immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) assays in 342 HCC patients. In addition, rapid amplification of complementary DNA ends-coupled PCR sequencing was performed, in order to confirm the presence of ALK abnormalities in patients exhibiting ALK messenger RNA (mRNA) overexpression. The correlation between ALK expression and the clinicopathological features and prognosis of the HCC patients was statistically analyzed. The results of the present study revealed overexpression of ALK protein and mRNA; furthermore, ALK gene copy number gains were observed via IHC (44.7%; 153/342), RT-qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, although ALK rearrangement or mutation was not demonstrated in the results of any of these assays. ALK protein expression levels were significantly associated with hepatitis C virus (HCV) status (P<0.001) and the presence of micrometastases (P=0.011). Within the entire patient cohort, ALK expression was associated with poor progression-free survival (PFS; P=0.041). Subsequent analysis in patient subgroups that demonstrated hepatitis B surface antigen positivity, HCV negativity, stage III–IV disease, recurrence and micrometastasis positivity revealed that overall survival (OS) and PFS were significantly reduced in those patients exhibiting ALK expression compared with those patients who were negative for ALK expression. Multivariate analysis revealed that ALK expression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III–IV tumors. Thus, ALK may serve as a novel indicator for the metastatic behavior and prognosis of HCC. D.A. Spandidos 2016-01 2015-11-04 /pmc/articles/PMC4727030/ /pubmed/26870191 http://dx.doi.org/10.3892/ol.2015.3859 Text en Copyright: © Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	LIU, JIANHUA JIN, HAOSHENG TIAN, HONGXIA LIAN, GUODA CHEN, SHAOJIE LI, JIAYU ZHANG, XUCHAO MA, DONG
spellingShingle	LIU, JIANHUA JIN, HAOSHENG TIAN, HONGXIA LIAN, GUODA CHEN, SHAOJIE LI, JIAYU ZHANG, XUCHAO MA, DONG Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
author_facet	LIU, JIANHUA JIN, HAOSHENG TIAN, HONGXIA LIAN, GUODA CHEN, SHAOJIE LI, JIAYU ZHANG, XUCHAO MA, DONG
author_sort	LIU, JIANHUA
title	Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
title_short	Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
title_full	Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
title_fullStr	Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
title_full_unstemmed	Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
title_sort	anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma
description	The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis. ALK status was investigated using immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) assays in 342 HCC patients. In addition, rapid amplification of complementary DNA ends-coupled PCR sequencing was performed, in order to confirm the presence of ALK abnormalities in patients exhibiting ALK messenger RNA (mRNA) overexpression. The correlation between ALK expression and the clinicopathological features and prognosis of the HCC patients was statistically analyzed. The results of the present study revealed overexpression of ALK protein and mRNA; furthermore, ALK gene copy number gains were observed via IHC (44.7%; 153/342), RT-qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, although ALK rearrangement or mutation was not demonstrated in the results of any of these assays. ALK protein expression levels were significantly associated with hepatitis C virus (HCV) status (P<0.001) and the presence of micrometastases (P=0.011). Within the entire patient cohort, ALK expression was associated with poor progression-free survival (PFS; P=0.041). Subsequent analysis in patient subgroups that demonstrated hepatitis B surface antigen positivity, HCV negativity, stage III–IV disease, recurrence and micrometastasis positivity revealed that overall survival (OS) and PFS were significantly reduced in those patients exhibiting ALK expression compared with those patients who were negative for ALK expression. Multivariate analysis revealed that ALK expression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III–IV tumors. Thus, ALK may serve as a novel indicator for the metastatic behavior and prognosis of HCC.
publisher	D.A. Spandidos
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727030/
_version_	1613528509838262272

Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma

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