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

Jeon AJ 1 , Teo YY 1 , Sekar K 1 , Chong SL 1 , Wu L 1 , Chew SC 1 Show all authors , Chen J 2 , Kendarsari RI 2 , Lai H 2 , Ling WH 1 , Kaya NA 2 , Lim JQ 2 , Ramasamy A 2 , Oguz G 2 , Chung AY 1 , Chan CY 1 , Cheow PC 1 , Kam JH 1 , Madhavan K 3 , Kow A 3 , Ganpathi IS 3 , Lim TKH 4 , Leow WQ 4 , Loong S 4 , Loh TJ 4 , Wan WK 4 , Soon GST 5 , Pang YH 5 , Yoong BK 6 , Ong DB 6 , Lim J 6 , de Villa VH 7 , Cruz RDD 8 , Chanwat R 9 , Thammasiri J 10 , Bonney GK 3 , Goh BKP 1 , Tucker-Kellogg G 11 , Foo RSY 2 , Chow PKH 12

Affiliations 

  • 1 Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore
  • 2 Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
  • 3 Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore
  • 4 Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore
  • 5 Department of Pathology, National University Hospital, Singapore, 119074, Singapore
  • 6 Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 7 Department of Surgery and Center for Liver Health and Transplantation, The Medical City, Pasig City, Metro Manila, Philippines
  • 8 Department of Laboratory Medicine and Pathology, The Medical City, Pasig City, Metro Manila, Philippines
  • 9 Hepato-Pancreato-Biliary Surgery Unit, Department of Surgery, National Cancer Institute, Bangkok, Thailand
  • 10 Division of Pathology, National Cancer Institute, Bangkok, Thailand
  • 11 Department of Biological Sciences, National University of Singapore, Singapore, Singapore
  • 12 Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore. pierce.chow@duke-nus.edu.sg
BMC Cancer, 2023 Feb 03;23(1):118.
PMID: 36737737 DOI: 10.1186/s12885-022-10444-3

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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