Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation

J Contreras-Mancilla; J P Cerapio; E Ruiz; R Fernández; S Casavilca-Zambrano; C Machicado; J J Fournié; P Pineau; S Bertani

doi:10.1016/j.rgmxen.2023.04.009

Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation

Rev Gastroenterol Mex (Engl Ed). 2023 May 8:S2255-534X(23)00044-0. doi: 10.1016/j.rgmxen.2023.04.009. Online ahead of print.

Authors

J Contreras-Mancilla¹, J P Cerapio², E Ruiz³, R Fernández³, S Casavilca-Zambrano³, C Machicado⁴, J J Fournié², P Pineau⁵, S Bertani⁶

Affiliations

¹ Laboratorio de Investigación Traslacional y Biología Computacional, Facultad de Ciencias y Filosofía - LID, Universidad Peruana Cayetano Heredia, Lima, Peru; Laboratorio Mixto Internacional de Oncología Antropológica Molecular (LOAM), IRD, INEN, Lima, Peru.
² Laboratorio Mixto Internacional de Oncología Antropológica Molecular (LOAM), IRD, INEN, Lima, Peru; Université de Toulouse, UMR 1037 CRCT, INSERM, CNRS, UPS, Toulouse, France; Laboratorio de Excelencia Toulouse-Cáncer (TOUCAN), Toulouse, France.
³ Laboratorio Mixto Internacional de Oncología Antropológica Molecular (LOAM), IRD, INEN, Lima, Peru; Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
⁴ Laboratorio de Investigación Traslacional y Biología Computacional, Facultad de Ciencias y Filosofía - LID, Universidad Peruana Cayetano Heredia, Lima, Peru; Instituto de Biocomputación y Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
⁵ Laboratorio Mixto Internacional de Oncología Antropológica Molecular (LOAM), IRD, INEN, Lima, Peru; Institut Pasteur, U 993, INSERM, Paris, France.
⁶ Laboratorio Mixto Internacional de Oncología Antropológica Molecular (LOAM), IRD, INEN, Lima, Peru; Université de Toulouse, UMR 152 PHARMADEV, IRD, UPS, Toulouse, France. Electronic address: stephane.bertani@ird.fr.

PMID: 37164797
DOI: 10.1016/j.rgmxen.2023.04.009

Abstract

Introduction and aim: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients.

Methods: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients.

Results: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (>90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients.

Conclusion: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.

Keywords: Carcinoma hepatocelular; DNA methylation; Hepatocellular carcinoma; Metilación del ADN; Peru; Perú; Transcriptoma; Transcriptome.