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秘鲁的肝细胞癌:一种非传统临床表现的分子描述。

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

作者信息

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

机构信息

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.

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.

出版信息

Rev Gastroenterol Mex (Engl Ed). 2024 Apr-Jun;89(2):194-204. doi: 10.1016/j.rgmxen.2023.04.009. Epub 2023 May 8.

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.

摘要

引言与目的

肝细胞癌(HCC)是秘鲁消化道肿瘤中第三常见的癌症,死亡率很高,每10万居民中有17.7人死亡。秘鲁相当一部分HCC病例并不遵循世界其他地区所描述的该疾病的经典临床流行病学特征。这些患者呈现出独特的转录组图谱和单一的肿瘤进程,提示秘鲁部分人群中存在一种特殊类型的肝癌发生机制。我们的目的是了解秘鲁患者HCC的表观遗传特征(甲基化)和基因表达(转录组)在临床和生物学方面的情况。

方法

对74名秘鲁患者的HCC和肝脏转录组及DNA甲基化图谱进行了评估。

结果

按年龄分组时,年轻的HCC患者DNA甲基化程度更高,但转录组图谱方面无差异。在年轻的HCC患者中还观察到乙肝病毒(HBV)的高流行率(>90%)。对两种分子图谱的富集分析均指出,PRC2是秘鲁患者肝脏肿瘤进程的重要分子效应器。

结论

秘鲁患者的HCC具有独特的分子特征,与HBV的存在以及与未分化肝细胞或细胞重编程相关的整体DNA高甲基化有关。

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