Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Jeon, Ah-Jung and Teo, Yue-Yang and Sekar, Karthik and Chong, Shay Lee and Wu, Lingyan and Chew, Sin-Chi and Chen, Jianbin and Kendarsari, Raden Indah and Lai, Hannah and Ling, Wen Huan and Kaya, Neslihan Arife and Lim, Jia Qi and Ramasamy, Adaikalavan and Oguz, Gokce and Chung, Alexander Yaw-Fui and Chan, Chung Yip and Cheow, Peng-Chung and Kam, Juinn Huar and Madhavan, Krishnakumar and Kow, Alfred and Ganpathi, Iyer Shridhar and Lim, Tony Kiat Hon and Leow, Wei-Qiang and Loong, Shihleone and Loh, Tracy Jiezhen and Wan, Wei Keat and Soon, Gwyneth Shook Ting and Pang, Yin Huei and Yoong, Boon Koon and Ong, Diana Bee-Lan and Lim, Jasmine and de Villa, Vanessa H. and dela Cruz, Rouchelle D. and Chanwat, Rawisak and Thammasiri, Jidapa and Bonney, Glenn K. and Goh, Brian K. P. and Tucker-Kellogg, Greg and Foo, Roger Sik Yin and Chow, Pierce K. H. (2023) Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma. BMC Cancer, 23 (1). ISSN 1471-2407, DOI https://doi.org/10.1186/s12885-022-10444-3.

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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.

Item Type: Article
Funders: Singapore National Medical Research Council Grants [Grant No: TCR/015-NCC/2016, CSA-SI/0018/2017 and CIRG18may-0057]
Uncontrolled Keywords: Multi-region sampling; Patient subgroups; Personalized medicine
Subjects: R Medicine > RD Surgery
Divisions: Faculty of Medicine > Surgery Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 12 Nov 2024 07:48
Last Modified: 12 Nov 2024 07:48
URI: http://eprints.um.edu.my/id/eprint/38647

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