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Molecular Scoring of Hepatocellular Carcinoma for Predicting Metastatic Recurrence and Requirements of Systemic Chemotherapy
- Source :
- Cancers, Vol 10, Iss 10, p 367 (2018), Cancers, Volume 10, Issue 10
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related deaths<br />an HCC subset shows rapid progression that affects survival. We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for TP53, CTNNB1, and TERT promoter mutation, methylation of 8 tumor suppressor genes, and 3 repetitive DNA sequences to estimate promoter hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was calculated to represent chromosomal instability through microsatellite analysis. Molecular subclasses were determined using corresponding and hierarchical clustering analyses. Next, twenty-five HCC patients who underwent liver transplantation were analyzed for associations between molecular characteristics and metastatic recurrence<br />survival analyses were validated using a publicly available dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). An HCC subtype characterized by TP53 mutation, high FAL, and global hypomethylation was associated with aggressive tumor characteristics, like vascular invasion<br />CTNNB1 mutation was a feature of the less-progressive phenotype. A number of molecular risk factors, including TP53 mutation, high FAL, significant global hypomethylation, and absence of CTNNB1 mutation, were noted to predict shorter recurrence-free survival in patients who underwent liver transplantation (p = 0.0090 by log-rank test). These findings were validated in a cohort of resected HCC cases from TCGA (p = 0.0076). We concluded that molecular risks determined by common genetic and epigenetic alterations could predict metastatic recurrence after curative treatments, and could be a marker for considering systemic therapy for HCC patients.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
recurrence
chromosomal alteration
medicine.medical_treatment
Liver transplantation
lcsh:RC254-282
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
Internal medicine
Chromosome instability
Medicine
systemic chemotherapy
Epigenetics
Gene
neoplasms
liver transplantation
business.industry
hepatocellular carcinoma
HCCS
medicine.disease
molecular subclass
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Phenotype
digestive system diseases
030104 developmental biology
Hepatocellular carcinoma
030211 gastroenterology & hepatology
methylation
mutation
business
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 10
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....f4cb48571eefcd14f86ce5c9268dd885