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

作者：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

来源：Oncotarget, 2017, 8(41): 71070-71079.

DOI：10.18632/oncotarget.20369

• hepatocellular carcinoma
• biomarker
• prognosis
• expression panel

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.

• 出版日期2017-9-19