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恒河猴肝脏发育过程中转录组与人类原发性肝癌甲胎蛋白相关基因表达的综合分析。

Integrated analysis of the rhesus monkey liver transcriptome during development and human primary HCC AFP-related gene expression.

作者信息

Feng Lin, Wang Yaru, Wang Xijun, An Songlin, Aizimuaji Zulihumaer, Tao Changcheng, Zhang Kai, Cheng Shujun, Wu Jianxiong, Xiao Ting, Rong Weiqi

机构信息

State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

出版信息

Mol Ther Nucleic Acids. 2021 Jun 24;25:406-415. doi: 10.1016/j.omtn.2021.06.004. eCollection 2021 Sep 3.

Abstract

Embryonic development and tumorigenesis have a certain degree of similarity. Alpha-fetoprotein (AFP), a protein related to embryonic development, is a well-known biomarker for the diagnosis and prognosis of hepatocellular carcinoma (HCC). In this study, we analyzed the differences in gene expression profiles and molecular mechanisms in human HCC tissues from patients in AFP (serum AFP level ≥ 25 ng/mL) and AFP (serum AFP level < 25 ng/mL) groups. The results indicated that AFP HCC has more malignant biological characteristics. Single-sample gene set enrichment analysis (ssGSEA) showed significantly higher levels of genes expressed in dendritic cells, neutrophils, and natural killer cells in the AFP group than in the AFP group. Then, we defined a rhesus monkey fetal liver developmental landscape and compared it to the HCC gene expression profile. The gene signatures of AFP HCC tissues were similar to those of early embryonic liver tissues. In this study, we comprehensively analyzed the rhesus monkey liver transcriptome during development and human primary HCC AFP-related gene expression profiles and clarified the function of AFP in the occurrence and development of HCC from the perspective of developmental biology, which might provide a new perspective on the pathogenesis of HCC.

摘要

胚胎发育与肿瘤发生具有一定程度的相似性。甲胎蛋白(AFP)是一种与胚胎发育相关的蛋白质,是肝细胞癌(HCC)诊断和预后的著名生物标志物。在本研究中,我们分析了AFP(血清AFP水平≥25 ng/mL)组和AFP(血清AFP水平<25 ng/mL)组患者的人HCC组织中基因表达谱和分子机制的差异。结果表明,AFP HCC具有更恶性的生物学特征。单样本基因集富集分析(ssGSEA)显示,AFP组中树突状细胞、中性粒细胞和自然杀伤细胞中表达的基因水平显著高于AFP组。然后,我们定义了恒河猴胎儿肝脏发育图谱,并将其与HCC基因表达谱进行比较。AFP HCC组织的基因特征与早期胚胎肝脏组织的基因特征相似。在本研究中,我们全面分析了恒河猴发育过程中的肝脏转录组和人类原发性HCC AFP相关基因表达谱,从发育生物学角度阐明了AFP在HCC发生发展中的作用,这可能为HCC的发病机制提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecfc/8403716/cefd0890ed97/fx1.jpg

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