秘鲁的肝细胞癌:非传统临床表现的分子描述

J. Contreras-Mancilla , J.P. Cerapio , E. Ruiz , R. Fernández , S. Casavilca-Zambrano , C. Machicado , J.J. Fournié , P. Pineau , S. Bertani
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引用次数: 0

摘要

引言和目的肝细胞癌(HCC)是秘鲁第三大最常见的消化道肿瘤癌症,死亡率高达每十万居民 17.7 例。秘鲁有大量的 HCC 病例与世界其他地区的典型临床流行病学不同。这些患者具有独特的转录组特征和独特的肿瘤过程,这表明秘鲁部分人群的肝癌发生类型比较特殊。我们的目的是了解秘鲁 HCC 患者的表观遗传学特征(甲基化)和基因表达(转录组)对临床和生物学的影响。结果按年龄分组后,年轻的 HCC 患者 DNA 甲基化程度更高,但转录组特征没有差异。在年轻的 HCC 患者中,乙型肝炎病毒(HBV)的感染率也很高(90%)。两种分子图谱的富集分析表明,PRC2是秘鲁患者肝脏肿瘤过程中的重要分子效应因子。结论 秘鲁患者的HCC具有独特的分子图谱,与HBV的存在以及与未分化肝细胞或细胞重编程有关的整体DNA高甲基化有关。
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Hepatocellular carcinoma in Peru: A molecular description of an unconventional clinical presentation

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.

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