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Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma
Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic fac...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073176/ https://www.ncbi.nlm.nih.gov/pubmed/31991869 http://dx.doi.org/10.3390/cancers12020293 |
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author | Chuma, Makoto Uojima, Haruki Numata, Kazushi Hidaka, Hisashi Toyoda, Hidenori Hiraoka, Atsushi Tada, Toshifumi Hirose, Shunji Atsukawa, Masanori Itokawa, Norio Arai, Taeang Kako, Makoto Nakazawa, Takahide Wada, Naohisa Iwasaki, Shuitirou Miura, Yuki Hishiki, Satoshi Nishigori, Shuhei Morimoto, Manabu Hattori, Nobuhiro Ogushi, Katsuaki Nozaki, Akito Fukuda, Hiroyuki Kagawa, Tatehiro Michitaka, Kojiro Kumada, Takashi Maeda, Shin |
author_facet | Chuma, Makoto Uojima, Haruki Numata, Kazushi Hidaka, Hisashi Toyoda, Hidenori Hiraoka, Atsushi Tada, Toshifumi Hirose, Shunji Atsukawa, Masanori Itokawa, Norio Arai, Taeang Kako, Makoto Nakazawa, Takahide Wada, Naohisa Iwasaki, Shuitirou Miura, Yuki Hishiki, Satoshi Nishigori, Shuhei Morimoto, Manabu Hattori, Nobuhiro Ogushi, Katsuaki Nozaki, Akito Fukuda, Hiroyuki Kagawa, Tatehiro Michitaka, Kojiro Kumada, Takashi Maeda, Shin |
author_sort | Chuma, Makoto |
collection | PubMed |
description | Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy. |
format | Online Article Text |
id | pubmed-7073176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70731762020-03-19 Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma Chuma, Makoto Uojima, Haruki Numata, Kazushi Hidaka, Hisashi Toyoda, Hidenori Hiraoka, Atsushi Tada, Toshifumi Hirose, Shunji Atsukawa, Masanori Itokawa, Norio Arai, Taeang Kako, Makoto Nakazawa, Takahide Wada, Naohisa Iwasaki, Shuitirou Miura, Yuki Hishiki, Satoshi Nishigori, Shuhei Morimoto, Manabu Hattori, Nobuhiro Ogushi, Katsuaki Nozaki, Akito Fukuda, Hiroyuki Kagawa, Tatehiro Michitaka, Kojiro Kumada, Takashi Maeda, Shin Cancers (Basel) Article Predictive biomarkers of the response of hepatocellular carcinoma (HCC) to Lenvatinib therapy have not yet been clarified. The aim of this study was to identify clinically significant biomarkers of response to Lenvatinib therapy, to target strategies against HCC. Levels of circulating angiogenic factors (CAFs) were analyzed in blood samples collected at baseline and after introducing lenvatinib, from 74 Child-Pugh class A HCC patients who received lenvatinib. As CAF biomarkers, serum vascular endothelial growth factor (VEGF), fibroblast growth factor 19 (FGF19), FGF23, and angiopoietin-2 (Ang-2) were measured using enzyme-linked immunosorbent assays. Results: Significantly increased FGF19 (FGF19-i) levels and decreased Ang-2 (Ang-2-d) levels were seen in Lenvatinib responders as compared to non-responders (ratio of FGF19 level at 4 weeks/baseline in responders vs. non-responders: 2.09 vs. 1.32, respectively, p = 0.0004; ratio of Ang-2 level at four weeks/baseline: 0.584 vs. 0.810, respectively, p = 0.0002). Changes in FGF23 and VEGF levels at four weeks versus baseline, however, were not significantly different in responders versus non-responders. In multivariate analysis, the combination of serum FGF19-i and Ang-2-d was the most independent predictive factor for Lenvatinib response (Odds ratio, 9.143; p = 0.0012). Furthermore, this combination biomarker showed the greatest independent association with progression-free survival (Hazard ratio, 0.171; p = 0.0240). Early changes in circulating FGF19 and Ang-2 levels might be useful for predicting clinical response and progression-free survival in HCC patients on Lenvatinib therapy. MDPI 2020-01-26 /pmc/articles/PMC7073176/ /pubmed/31991869 http://dx.doi.org/10.3390/cancers12020293 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chuma, Makoto Uojima, Haruki Numata, Kazushi Hidaka, Hisashi Toyoda, Hidenori Hiraoka, Atsushi Tada, Toshifumi Hirose, Shunji Atsukawa, Masanori Itokawa, Norio Arai, Taeang Kako, Makoto Nakazawa, Takahide Wada, Naohisa Iwasaki, Shuitirou Miura, Yuki Hishiki, Satoshi Nishigori, Shuhei Morimoto, Manabu Hattori, Nobuhiro Ogushi, Katsuaki Nozaki, Akito Fukuda, Hiroyuki Kagawa, Tatehiro Michitaka, Kojiro Kumada, Takashi Maeda, Shin Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title | Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title_full | Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title_fullStr | Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title_full_unstemmed | Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title_short | Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma |
title_sort | early changes in circulating fgf19 and ang-2 levels as possible predictive biomarkers of clinical response to lenvatinib therapy in hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073176/ https://www.ncbi.nlm.nih.gov/pubmed/31991869 http://dx.doi.org/10.3390/cancers12020293 |
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