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

ABSTRACT: 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.

SUBMITTER: Kanda M

PROVIDER: S-EPMC5642618 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Kanda Mitsuro M Murotani Kenta K Sugimoto Hiroyuki H Miwa Takashi T Umeda Shinichi S Suenaga Masaya M Hayashi Masamichi M Hattori Norifumi N Tanaka Chie C Kobayashi Daisuke D Yamada Suguru S Fujiwara Michitaka M Kodera Yasuhiro Y

Oncotarget 20170819 41

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 ...[more]

PMID: 29050343

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Project description:Abstract Background Post-hepatectomy liver failure (PHLF) is one of the most serious postoperative complications after hepatectomy. The aim of this study was to assess the impact of the International Study Group of Liver Surgery (ISGLS) definition of PHLF on morbidity and short- and long-term survival after major hepatectomy. Methods This was a retrospective review of all patients who underwent major hepatectomy (three or more liver segments) for various liver tumours between 2010 and 2018 at two Swedish tertiary centres for hepatopancreatobiliary surgery. Descriptive statistics, regression models, and survival analyses were used. Results A total of 799 patients underwent major hepatectomy, of which 218 patients (27 per cent) developed ISGLS-defined PHLF, including 115 patients (14 per cent) with ISGLS grade A, 76 patients (10 per cent) with grade B, and 27 patients (3 per cent) with grade C. The presence of cirrhosis, perihilar cholangiocarcinoma, and gallbladder cancer, right-sided hemihepatectomy and trisectionectomy all significantly increased the risk of clinically relevant PHLF (grades B and C). Clinically relevant PHLF increased the risk of 90-day mortality and was associated with impaired long-term survival. ISGLS grade A had more major postoperative complications compared with no PHLF but failed to be an independent predictor of both 90-day mortality and long-term survival. The impact of PHLF grade B/C on long-term survival was no longer present in patients surviving the first 90 days after surgery. Conclusions The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival; however, even ISGLS grade A had clinical implications. The aim was to assess the ISGLS criteria for post-hepatectomy liver failure (PHLF) in a cohort of patients with major hepatectomy. The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival.

Dataset Information

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

Publications

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

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