Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer

Abstract Based on our previous phase II clinical trial of anti-programmed death-1 (PD-1) antibody nivolumab for platinum-resistant ovarian cancer (n = 19, UMIN000005714), we aimed to identify the biomarkers predictive of response. Tumor gene expression was evaluated by proliferative, mesenchymal, di...

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Autores principales:	Ryusuke Murakami, Junzo Hamanishi, J. B. Brown, Kaoru Abiko, Koji Yamanoi, Mana Taki, Yuko Hosoe, Ken Yamaguchi, Tsukasa Baba, Noriomi Matsumura, Ikuo Konishi, Masaki Mandai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2172fc8b2d534ff6b34b0f655aab8608
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spelling	oai:doaj.org-article:2172fc8b2d534ff6b34b0f655aab86082021-12-02T15:57:11ZCombination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer10.1038/s41598-021-91012-w2045-2322https://doaj.org/article/2172fc8b2d534ff6b34b0f655aab86082021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91012-whttps://doaj.org/toc/2045-2322Abstract Based on our previous phase II clinical trial of anti-programmed death-1 (PD-1) antibody nivolumab for platinum-resistant ovarian cancer (n = 19, UMIN000005714), we aimed to identify the biomarkers predictive of response. Tumor gene expression was evaluated by proliferative, mesenchymal, differentiated, and immunoreactive gene signatures derived from high-grade serous carcinomas and a signature established prior for ovarian clear cell carcinoma. Resulting signature scores were statistically assessed with both univariate and multivariate approaches for correlation to clinical response. Analyses were performed to identify pathways differentially expressed by either the complete response (CR) or progressive disease (PD) patient groups. The clear cell gene signature was scored significantly higher in the CR group, and the proliferative gene signature had significantly higher scores in the PD group where nivolumab was not effective (respective p values 0.005 and 0.026). Combinations of gene signatures improved correlation with response, where a visual projection of immunoreactive, proliferative, and clear cell signatures differentiated clinical response. An applicable clinical response prediction formula was derived. Ovarian cancer-specific gene signatures and related pathway scores provide a robust preliminary indicator for ovarian cancer patients prior to anti-PD-1 therapy decisions.Ryusuke MurakamiJunzo HamanishiJ. B. BrownKaoru AbikoKoji YamanoiMana TakiYuko HosoeKen YamaguchiTsukasa BabaNoriomi MatsumuraIkuo KonishiMasaki MandaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryusuke Murakami Junzo Hamanishi J. B. Brown Kaoru Abiko Koji Yamanoi Mana Taki Yuko Hosoe Ken Yamaguchi Tsukasa Baba Noriomi Matsumura Ikuo Konishi Masaki Mandai Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
description	Abstract Based on our previous phase II clinical trial of anti-programmed death-1 (PD-1) antibody nivolumab for platinum-resistant ovarian cancer (n = 19, UMIN000005714), we aimed to identify the biomarkers predictive of response. Tumor gene expression was evaluated by proliferative, mesenchymal, differentiated, and immunoreactive gene signatures derived from high-grade serous carcinomas and a signature established prior for ovarian clear cell carcinoma. Resulting signature scores were statistically assessed with both univariate and multivariate approaches for correlation to clinical response. Analyses were performed to identify pathways differentially expressed by either the complete response (CR) or progressive disease (PD) patient groups. The clear cell gene signature was scored significantly higher in the CR group, and the proliferative gene signature had significantly higher scores in the PD group where nivolumab was not effective (respective p values 0.005 and 0.026). Combinations of gene signatures improved correlation with response, where a visual projection of immunoreactive, proliferative, and clear cell signatures differentiated clinical response. An applicable clinical response prediction formula was derived. Ovarian cancer-specific gene signatures and related pathway scores provide a robust preliminary indicator for ovarian cancer patients prior to anti-PD-1 therapy decisions.
format	article
author	Ryusuke Murakami Junzo Hamanishi J. B. Brown Kaoru Abiko Koji Yamanoi Mana Taki Yuko Hosoe Ken Yamaguchi Tsukasa Baba Noriomi Matsumura Ikuo Konishi Masaki Mandai
author_facet	Ryusuke Murakami Junzo Hamanishi J. B. Brown Kaoru Abiko Koji Yamanoi Mana Taki Yuko Hosoe Ken Yamaguchi Tsukasa Baba Noriomi Matsumura Ikuo Konishi Masaki Mandai
author_sort	Ryusuke Murakami
title	Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
title_short	Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
title_full	Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
title_fullStr	Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
title_full_unstemmed	Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
title_sort	combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2172fc8b2d534ff6b34b0f655aab8608
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Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer

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