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

Autor: Jeon AJ; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Teo YY; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Sekar K; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Chong SL; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Wu L; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Chew SC; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Chen J; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Kendarsari RI; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Lai H; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Ling WH; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore., Kaya NA; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Lim JQ; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Ramasamy A; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Oguz G; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Chung AY; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore., Chan CY; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore., Cheow PC; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore., Kam JH; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore., Madhavan K; Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Kow A; Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Ganpathi IS; Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Lim TKH; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore., Leow WQ; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore., Loong S; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore., Loh TJ; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore., Wan WK; Department of Anatomical Pathology, Singapore General Hospital, Singapore, 169608, Singapore., Soon GST; Department of Pathology, National University Hospital, Singapore, 119074, Singapore., Pang YH; Department of Pathology, National University Hospital, Singapore, 119074, Singapore., Yoong BK; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Ong DB; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Lim J; Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., de Villa VH; Department of Surgery and Center for Liver Health and Transplantation, The Medical City, Pasig City, Metro Manila, Philippines., Cruz RDD; Department of Laboratory Medicine and Pathology, The Medical City, Pasig City, Metro Manila, Philippines., Chanwat R; Hepato-Pancreato-Biliary Surgery Unit, Department of Surgery, National Cancer Institute, Bangkok, Thailand., Thammasiri J; Division of Pathology, National Cancer Institute, Bangkok, Thailand., Bonney GK; Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Goh BKP; Department of Hepatopancreatobiliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and National Cancer Centre Singapore, Singapore, Singapore.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore., Tucker-Kellogg G; Department of Biological Sciences, National University of Singapore, Singapore, Singapore., Foo RSY; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chow PKH; 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.; Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, Singapore, Singapore. pierce.chow@duke-nus.edu.sg.; Academic Clinical Programme for Surgery, Duke-NUS Medical School, Singapore, Singapore. pierce.chow@duke-nus.edu.sg.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2023 Feb 03; Vol. 23 (1), pp. 118. Date of Electronic Publication: 2023 Feb 03.
DOI: 10.1186/s12885-022-10444-3
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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