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Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma

机译:RASSF1A减少在肝细胞癌中的表达及高甲基化的临床病理学意义

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PurposeProtein downregulation and hypermethylation of Ras association domain family 1A (RASSF1A) has been recognized as an important early event in different classes of carcinogenesis, but clinicopathological significance of RASSF1A protein expression and methylation in hepatocellular carcinoma (HCC) remains largely unknown. The aim of the study was to investigate the expression of RASSF1A protein and methylation in HCC and their clinical significance.MethodsImmunohistochemistry was employed to detect the expression of RASSF1A proteins in liver tissue microarrays. Aberrant promoter hypermethylation of RASSF1A was investigated in DNA from HCC, matching noncancerous tissues and serum of 35 HCC patients by methylation-specific PCR.ResultsRASSF1A protein expression in HCC was significantly lower than that in noncancerous (p?=?0.015) and paracancerous tissues (p?=?0.017). In addition, reduced RASSF1A protein expression is related to TNM stage, metastasis, α-fetoprotein, portal vein embolus, capsular infiltration, and multiple tumor nodes. Furthermore, RASSF1A promoter methylation in HCC was significantly higher than that in noncancerous liver tissues (p?
机译:目的蛋白的下调和Ras关联结构域家族1A(RASSF1A)的高甲基化已被认为是不同类别的癌变中的重要早期事件,但是RASSF1A蛋白表达和甲基化在肝细胞癌(HCC)中的临床病理学意义仍然未知。本研究的目的是研究肝癌组织中RASSF1A蛋白和甲基化的表达及其临床意义。方法采用免疫组织化学方法检测肝组织微阵列中RASSF1A蛋白的表达。通过甲基化特异性PCR在35例HCC患者的肝癌DNA,匹配的非癌组织和血清中检测到RASSF1A异常启动子的超甲基化,结果HCC中RASSF1A蛋白的表达显着低于非癌(p?=?0.015)和癌旁组织( p≥0.017)。此外,RASSF1A蛋白表达降低与TNM分期,转移,甲胎蛋白,门静脉栓塞,荚膜浸润和多个肿瘤结节有关。此外,肝癌中RASSF1A启动子甲基化明显高于非癌性肝组织(p <0.05)。同时,在HCC患者血清DNA中的14个中检测到RASSF1A启动子超甲基化,而在正常对照中未检测到超甲基化。 HCC血清和组织中RASSF1A的高甲基化与RASSF1A蛋白的表达呈负相关(p?<?0.05)。结论RASSF1A的丢失或异常蛋白下调和启动子的高甲基化可能在肝癌的发生,发展和转移中起重要作用。 。血清DNA中RASSF1A启动子高甲基化的检测可能是对高风险HCC人群进行早期诊断的有价值的生物标记。

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