Cargando…

Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma

By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify o...

Descripción completa

Detalles Bibliográficos
Autores principales: Cheng, Shu-Wen, Tsai, Hung-Wen, Lin, Yih-Jyh, Cheng, Pin-Nan, Chang, Yu-Chung, Yen, Chia-Jui, Huang, Hsuan-Pang, Chuang, Yun-Pei, Chang, Ting-Tsung, Lee, Chung-Ta, Chao, Anning, Chou, Cheng-Yang, Chan, Shih-Huang, Chow, Nan-Haw, Ho, Chung-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828221/
https://www.ncbi.nlm.nih.gov/pubmed/24244607
http://dx.doi.org/10.1371/journal.pone.0080053
_version_ 1782291201954676736
author Cheng, Shu-Wen
Tsai, Hung-Wen
Lin, Yih-Jyh
Cheng, Pin-Nan
Chang, Yu-Chung
Yen, Chia-Jui
Huang, Hsuan-Pang
Chuang, Yun-Pei
Chang, Ting-Tsung
Lee, Chung-Ta
Chao, Anning
Chou, Cheng-Yang
Chan, Shih-Huang
Chow, Nan-Haw
Ho, Chung-Liang
author_facet Cheng, Shu-Wen
Tsai, Hung-Wen
Lin, Yih-Jyh
Cheng, Pin-Nan
Chang, Yu-Chung
Yen, Chia-Jui
Huang, Hsuan-Pang
Chuang, Yun-Pei
Chang, Ting-Tsung
Lee, Chung-Ta
Chao, Anning
Chou, Cheng-Yang
Chan, Shih-Huang
Chow, Nan-Haw
Ho, Chung-Liang
author_sort Cheng, Shu-Wen
collection PubMed
description By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC.
format Online
Article
Text
id pubmed-3828221
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38282212013-11-16 Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma Cheng, Shu-Wen Tsai, Hung-Wen Lin, Yih-Jyh Cheng, Pin-Nan Chang, Yu-Chung Yen, Chia-Jui Huang, Hsuan-Pang Chuang, Yun-Pei Chang, Ting-Tsung Lee, Chung-Ta Chao, Anning Chou, Cheng-Yang Chan, Shih-Huang Chow, Nan-Haw Ho, Chung-Liang PLoS One Research Article By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC. Public Library of Science 2013-11-14 /pmc/articles/PMC3828221/ /pubmed/24244607 http://dx.doi.org/10.1371/journal.pone.0080053 Text en © 2013 Cheng et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cheng, Shu-Wen
Tsai, Hung-Wen
Lin, Yih-Jyh
Cheng, Pin-Nan
Chang, Yu-Chung
Yen, Chia-Jui
Huang, Hsuan-Pang
Chuang, Yun-Pei
Chang, Ting-Tsung
Lee, Chung-Ta
Chao, Anning
Chou, Cheng-Yang
Chan, Shih-Huang
Chow, Nan-Haw
Ho, Chung-Liang
Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title_full Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title_fullStr Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title_full_unstemmed Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title_short Lin28B Is an Oncofetal Circulating Cancer Stem Cell-Like Marker Associated with Recurrence of Hepatocellular Carcinoma
title_sort lin28b is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828221/
https://www.ncbi.nlm.nih.gov/pubmed/24244607
http://dx.doi.org/10.1371/journal.pone.0080053
work_keys_str_mv AT chengshuwen lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT tsaihungwen lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT linyihjyh lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chengpinnan lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT changyuchung lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT yenchiajui lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT huanghsuanpang lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chuangyunpei lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT changtingtsung lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT leechungta lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chaoanning lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chouchengyang lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chanshihhuang lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT chownanhaw lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma
AT hochungliang lin28bisanoncofetalcirculatingcancerstemcelllikemarkerassociatedwithrecurrenceofhepatocellularcarcinoma