Sant'Anna Thaís Barbosa Ferreira, Terra Mariana Leonardo, de Barros Jose Junior França, Ruivo Leonardo Alexandre de Souza, Fernandes Arlete, Begnami Maria Dirlei Ferreira de Souza, Pannain Vera Lucia Nunes, Campos Antônio Hugo José Fróes Marques, Moreira Otacilio da Cruz, de Araujo Natalia Motta
Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil.
Department of Pathology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil.
Int J Mol Sci. 2025 Jul 6;26(13):6503. doi: 10.3390/ijms26136503.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, but its molecular drivers remain underexplored in Latin American populations. This study investigated the prevalence, co-occurrence, and tissue distribution of somatic mutations in the promoter (C228T/C250T) and exon 3, as well as gene expression, in liver tissues from Brazilian patients. A total of 85 samples (42 HCC, 21 cirrhosis, and 22 hepatitis) were analysed using Sanger sequencing and RT-qPCR. promoter mutations were detected in 47.6% of HCC tissues, including C228T (45.2%) and C250T (2.4%), and were also present in 19% of cirrhotic tissues but absent in hepatitis samples, supporting their emergence in early hepatocarcinogenesis. exon 3 mutations occurred in 17.2% of HCCs and significantly co-occurred with mutations (66.7%, = 0.0485), although the number of -mutated cases was limited. expression was significantly upregulated in HCC tissues regardless of mutation status ( < 0.001). This is the first study to characterise these mutations in Brazilian HCC patients, highlighting the C228T mutation as a promising biomarker for early detection and molecular surveillance in cirrhotic individuals. Despite the genetic admixture of the studied population, the mutational patterns were comparable to those reported in more homogeneous populations, reinforcing the global relevance of these molecular alterations.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因，但其分子驱动因素在拉丁美洲人群中仍未得到充分研究。本研究调查了巴西患者肝脏组织中启动子（C228T/C250T）和外显子3体细胞突变的发生率、共发生情况和组织分布，以及基因表达。使用桑格测序和RT-qPCR分析了总共85个样本（42个HCC、21个肝硬化和22个肝炎样本）。在47.6%的HCC组织中检测到启动子突变，包括C228T（45.2%）和C250T（2.4%），在19%的肝硬化组织中也存在，但在肝炎样本中不存在，这支持了它们在早期肝癌发生过程中出现。17.2%的HCC发生外显子3突变，并且与启动子突变显著共发生（66.7%，P = 0.0485），尽管启动子突变病例数量有限。无论突变状态如何，HCC组织中的基因表达均显著上调（P < 0.001）。这是第一项对巴西HCC患者中的这些突变进行特征描述的研究，突出了C228T突变作为肝硬化个体早期检测和分子监测的有前景的生物标志物。尽管所研究人群存在遗传混合，但突变模式与在更同质人群中报道的模式相当，强化了这些分子改变的全球相关性。
