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Published on: September 30, 2021
Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation
J Contreras-Mancilla1, J P Cerapio2, E Ruiz3
1Laboratorio 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.
Insights
Peruvian patients with hepatocellular carcinoma (HCC) show unique molecular profiles, including increased DNA methylation in younger individuals and a high prevalence of hepatitis B virus (HBV). These findings suggest a distinct form of liver cancer development in this population.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Hepatocellular carcinoma (HCC) is a significant health concern in Peru, with a distinct clinical epidemiology.
- A notable subset of Peruvian HCC cases exhibits unique transcriptome profiles and tumor processes, suggesting a specific hepatocarcinogenesis pathway.
- Understanding the epigenetic and transcriptomic landscape is crucial for characterizing these distinct HCC cases.
Purpose of the Study:
- To investigate the clinical and biological involvement of epigenetic (DNA methylation) and gene expression (transcriptome) profiles in Peruvian HCC patients.
- To elucidate the unique molecular characteristics of HCC in the Peruvian population.
- To identify potential molecular effectors driving hepatocarcinogenesis in Peru.
Main Methods:
- Evaluation of liver transcriptome and DNA methylation profiles in 74 Peruvian HCC patients.
- Comparative analysis of molecular profiles based on patient age.
- Enrichment analyses to identify key molecular pathways and effectors.
Main Results:
- Younger Peruvian HCC patients exhibited greater DNA methylation compared to older patients.
- A high prevalence (>90%) of hepatitis B virus (HBV) infection was observed in younger HCC patients.
- Enrichment analyses identified PRC2 as a significant molecular effector in the liver tumor process of Peruvian patients.
Conclusions:
- Hepatocellular carcinoma in Peruvian patients presents a unique molecular signature.
- This unique profile is associated with the presence of hepatitis B virus (HBV).
- Elevated DNA hypermethylation is linked to undifferentiated liver cells or cellular reprogramming in Peruvian HCC.
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.
