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An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1:2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate...

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Autores principales: Kanda, Mitsuro, Murotani, Kenta, Sugimoto, Hiroyuki, Miwa, Takashi, Umeda, Shinichi, Suenaga, Masaya, Hayashi, Masamichi, Hattori, Norifumi, Tanaka, Chie, Kobayashi, Daisuke, Yamada, Suguru, Fujiwara, Michitaka, Kodera, Yasuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642618/
https://www.ncbi.nlm.nih.gov/pubmed/29050343
http://dx.doi.org/10.18632/oncotarget.20369
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author Kanda, Mitsuro
Murotani, Kenta
Sugimoto, Hiroyuki
Miwa, Takashi
Umeda, Shinichi
Suenaga, Masaya
Hayashi, Masamichi
Hattori, Norifumi
Tanaka, Chie
Kobayashi, Daisuke
Yamada, Suguru
Fujiwara, Michitaka
Kodera, Yasuhiro
author_facet Kanda, Mitsuro
Murotani, Kenta
Sugimoto, Hiroyuki
Miwa, Takashi
Umeda, Shinichi
Suenaga, Masaya
Hayashi, Masamichi
Hattori, Norifumi
Tanaka, Chie
Kobayashi, Daisuke
Yamada, Suguru
Fujiwara, Michitaka
Kodera, Yasuhiro
author_sort Kanda, Mitsuro
collection PubMed
description Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1:2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate molecular markers were determined using quantitative reverse-transcriptase PCR. In the discovery set, an expression panel was developed according to the concordance index (C-index) values for overall survival from all 4095 combinations of the 12 candidate molecular markers. Expression scores was determined with weighting according to the coefficient in a Cox regression, and patients were classified into grade 1, 2 and 3. Reproducibility was then tested in the validation set. A panel consisting of four markers, PRMT5, MAGED4, DPYSL3 and AJAP1 was selected as the optimal and most well-balanced set with a C-index value of 0.707. Patient prognosis was clearly stratified by the expression grade using this panel. In the validation set, both overall and disease-free survival rates decreased incrementally with as the grade increased. Higher grades were significantly associated with tumor multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was increased in grade 3 patients. The integrated multigene expression panel clearly stratified HCC patients into low, intermediate and high risk.
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spelling pubmed-56426182017-10-18 An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma Kanda, Mitsuro Murotani, Kenta Sugimoto, Hiroyuki Miwa, Takashi Umeda, Shinichi Suenaga, Masaya Hayashi, Masamichi Hattori, Norifumi Tanaka, Chie Kobayashi, Daisuke Yamada, Suguru Fujiwara, Michitaka Kodera, Yasuhiro Oncotarget Research Paper Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1:2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate molecular markers were determined using quantitative reverse-transcriptase PCR. In the discovery set, an expression panel was developed according to the concordance index (C-index) values for overall survival from all 4095 combinations of the 12 candidate molecular markers. Expression scores was determined with weighting according to the coefficient in a Cox regression, and patients were classified into grade 1, 2 and 3. Reproducibility was then tested in the validation set. A panel consisting of four markers, PRMT5, MAGED4, DPYSL3 and AJAP1 was selected as the optimal and most well-balanced set with a C-index value of 0.707. Patient prognosis was clearly stratified by the expression grade using this panel. In the validation set, both overall and disease-free survival rates decreased incrementally with as the grade increased. Higher grades were significantly associated with tumor multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was increased in grade 3 patients. The integrated multigene expression panel clearly stratified HCC patients into low, intermediate and high risk. Impact Journals LLC 2017-08-19 /pmc/articles/PMC5642618/ /pubmed/29050343 http://dx.doi.org/10.18632/oncotarget.20369 Text en Copyright: © 2017 Kanda et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kanda, Mitsuro
Murotani, Kenta
Sugimoto, Hiroyuki
Miwa, Takashi
Umeda, Shinichi
Suenaga, Masaya
Hayashi, Masamichi
Hattori, Norifumi
Tanaka, Chie
Kobayashi, Daisuke
Yamada, Suguru
Fujiwara, Michitaka
Kodera, Yasuhiro
An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title_full An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title_fullStr An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title_full_unstemmed An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title_short An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
title_sort integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642618/
https://www.ncbi.nlm.nih.gov/pubmed/29050343
http://dx.doi.org/10.18632/oncotarget.20369
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