학술논문
Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma
Document Type
Original Paper
Author
Jeon, Ah-Jung; Teo, Yue-Yang; Sekar, Karthik; Chong, Shay Lee; Wu, Lingyan; Chew, Sin-Chi; Chen, Jianbin; Kendarsari, Raden Indah; Lai, Hannah; Ling, Wen Huan; Kaya, Neslihan Arife; Lim, Jia Qi; Ramasamy, Adaikalavan; Oguz, Gokce; Chung, Alexander Yaw-Fui; Chan, Chung Yip; Cheow, Peng-Chung; Kam, Juinn Huar; Madhavan, Krishnakumar; Kow, Alfred; Ganpathi, Iyer Shridhar; Lim, Tony Kiat Hon; Leow, Wei-Qiang; Loong, Shihleone; Loh, Tracy Jiezhen; Wan, Wei Keat; Soon, Gwyneth Shook Ting; Pang, Yin Huei; Yoong, Boon Koon; Ong, Diana Bee-Lan; Lim, Jasmine; de Villa, Vanessa H.; Cruz, Rouchelle D.dela; Chanwat, Rawisak; Thammasiri, Jidapa; Bonney, Glenn K.; Goh, Brian K. P.; Tucker-Kellogg, Greg; Foo, Roger Sik Yin; Chow, Pierce K. H.
Source
BMC Cancer. 23(1)
Subject
Language
English
ISSN
1471-2407
Abstract
Background: Conventional 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).Methods: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients’ matched adjacent normal samples.Results: Comparing 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/conclusion: Our 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.