Format

Send to

Choose Destination
BMC Cancer. 2018 May 18;18(1):571. doi: 10.1186/s12885-018-4192-1.

The clinical implications of G1-G6 transcriptomic signature and 5-gene score in Korean patients with hepatocellular carcinoma.

Ahn SM1,2, Haq F3, Park I1, Nault JC4,5,6,7, Zucman-Rossi J8,9,10,11, Yu E12.

Author information

1
Department of Genome Medicine and Science, College of Medicine, Gachon University, Seongnam, South Korea.
2
Department of Hematology-Oncology, Gachon University Gil Hospital, Incheon, South Korea.
3
Department of Biosciences, Cancer Genetics and Epigenetics Lab, COMSATS Institute of Information Technology, Islamabad, Pakistan.
4
Inserm, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Équipe Labellisée Ligue Contre le Cancer, 27 rue Juliette Dodu, F-75010, Paris, France.
5
Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.
6
Sorbonne Paris Cité, UFR SMBH, Université Paris 13, F-93000, Bobigny, France.
7
Université Paris Diderot, F-75013, Paris, France.
8
Inserm, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Équipe Labellisée Ligue Contre le Cancer, 27 rue Juliette Dodu, F-75010, Paris, France. jessica.zucman-rossi@inserm.fr.
9
Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France. jessica.zucman-rossi@inserm.fr.
10
Sorbonne Paris Cité, UFR SMBH, Université Paris 13, F-93000, Bobigny, France. jessica.zucman-rossi@inserm.fr.
11
Université Paris Diderot, F-75013, Paris, France. jessica.zucman-rossi@inserm.fr.
12
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, OLYMPIC-RO 43-GIL, SONGPA-GU, SEOUL, 138-736, South Korea. esyu@amc.seoul.kr.

Abstract

BACKGROUND:

Efforts have been made to classify Hepatocellular Carcinoma (HCC) at surgically curable stages because molecular classification, which is prognostically informative, can accurately identify patients in need of additional early therapeutic interventions. Recently, HCC classification based French studies on the expression of 16 genes and 5 genes were proposed. In 16-gene classification, transcriptomic signatures (G1-G6) were used to classify HCC patients into clinical, genomic and pathway-specific subgroups. In 5-gene score classification, the good or poor prognosis of HCC patients was predicted. The patient's cohort in these studies was mainly from Caucasian and African populations. Here, we aimed to validate G1-G6 and 5-gene score signatures in 205 Korean HCC patients since genomic profiles of Korean patients are distinct from other regions.

METHODS:

Integrated analyses using whole-exome sequencing, copy number variation and clinical data was performed against these two signatures to find statistical correlations. Kaplan-Meier, univariate and multivariate COX regression analysis were performed for Disease-Specific Survival (DSS) and Recurrence-Free Survival (RFS).

RESULTS:

The G2 and G3 subgroups of transcriptomic signature were significantly associated with TP53 mutations while G5 and G6 subgroups were significantly associated with CTNNB1 mutations which is in concordance with original French studies. Similarly, the poor prognosis group of 5-gene score showed shorter DSS (p = 0.045) and early RFS (p = 0.023) as well as a significant association with microvascular invasion, tumor size (> 5 cm), elevated AFP levels, and RB1 mutations. However, the 5-gene score was not an independent prognostic factor for survival.

CONCLUSION:

The G1-G6 and 5-gene signatures showed significant concordance between genetic profiles of Korean HCC patients and patients in original French studies. Thus, G1-G6 and 5-gene score signatures can be targeted as potential therapeutic biomarkers against HCC patients worldwide.

KEYWORDS:

5-gene score; G1-G6 subgroups; Prognosis; Survival

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center