Research Papers:

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

Mitsuro Kanda _, Kenta Murotani, Hiroyuki Sugimoto, Takashi Miwa, Shinichi Umeda, Masaya Suenaga, Masamichi Hayashi, Norifumi Hattori, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Michitaka Fujiwara and Yasuhiro Kodera

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Oncotarget. 2017; 8:71070-71079. https://doi.org/10.18632/oncotarget.20369

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Mitsuro Kanda1, Kenta Murotani2, Hiroyuki Sugimoto1, Takashi Miwa1, Shinichi Umeda1, Masaya Suenaga1, Masamichi Hayashi1, Norifumi Hattori1, Chie Tanaka1, Daisuke Kobayashi1, Suguru Yamada1, Michitaka Fujiwara1 and Yasuhiro Kodera1

1Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

2Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan

Correspondence to:

Mitsuro Kanda, email: [email protected]

Keywords: hepatocellular carcinoma, biomarker, prognosis, expression panel

Received: June 22, 2017     Accepted: July 25, 2017     Published: August 19, 2017


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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