Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma
Document Type
Article
Publication Date
2-1-2023
Abstract
BackgroundConventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).MethodsUsing multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.ResultsComparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.Discussion/conclusionOur results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
Keywords
Multi-region sampling, Patient subgroups, Personalized medicine
Divisions
surgerydept
Funders
Singapore National Medical Research Council Grants [Grant No: TCR/015-NCC/2016, CSA-SI/0018/2017 and CIRG18may-0057]
Publication Title
BMC Cancer
Volume
23
Issue
1
Publisher
BioMed Central
Publisher Location
CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND