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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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