与肝细胞癌相关的位点特异性人内源性逆转录病毒表达。
Locus-specific HERV expression associated with hepatocellular carcinoma.
作者信息
Wen Hui, Pérez-Losada Marcos, Mishra Lopa, Crandall Keith A
机构信息
Computational Biology Institute and Department of Biostatistics & Bioinformatics, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.
The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, 20852, USA.
出版信息
Mob DNA. 2025 Jul 16;16(1):30. doi: 10.1186/s13100-025-00367-8.
BACKGROUND
Human endogenous retroviruses (HERVs) harbor accessory proteins that influence cellular processes and have been linked to a wide variety of diseases, including cancer. This study investigates locus-specific HERV expression and its association with gene dysregulation in hepatocellular carcinoma (HCC), a highly prevalent and deadly form of liver cancer worldwide.
METHODS
We analyzed RNASeq data from 424 HCC samples from The Cancer Genome Atlas (TCGA), which comprised 371 tumor and 50 matched normal tissues from a total of 371 hepatocellular carcinoma participants. We employed Telescope to identify and quantify HERV expression across the total RNA sequencing data.
RESULTS
The majority of differentially expressed HERVs exhibited reduced expression in tumor tissue (166 downregulated vs. 50 upregulated), suggesting a potential functional role of HERV expression patterns in shaping the pathophysiological landscape of HCC. Specifically, the suppression of HERV-H family members, which are known to regulate cellular differentiation, may contribute to tumor dedifferentiation, increased plasticity, and enhanced metastatic potential. This loss of differentiation control and increased adaptability may play a critical role in driving the progression of liver cancer.
DISCUSSION
Our study highlights a significant association of HERV expression with HCC, highlighting the differential regulation of specific HERV families in tumor tissue. For example, HERVH and ERVLE families showed consistent downregulation in tumor samples, while HERVE and HERV9 were more commonly upregulated. These shifts may reflect underlying changes in transcriptional regulation or chromatin structure between normal and malignant tissues. Rather than indicating a singular functional role, the observed expression patterns likely reflect a multifaceted relationship between HERVs and tumor biology. Further studies will be needed to determine whether these expression differences contribute to, or result from, tumor progression and to explore their potential as biomarkers or therapeutic targets.
CLINICAL TRIAL NUMBER
Not applicable.
背景
人类内源性逆转录病毒（HERV）含有影响细胞进程的辅助蛋白，并与包括癌症在内的多种疾病相关。本研究调查了肝细胞癌（HCC）中特定基因座的HERV表达及其与基因失调的关联，HCC是全球范围内一种高度流行且致命的肝癌形式。
方法
我们分析了来自癌症基因组图谱（TCGA）的424份HCC样本的RNA测序数据，其中包括来自371名肝细胞癌参与者的371份肿瘤组织和50份匹配的正常组织。我们使用Telescope在整个RNA测序数据中识别和量化HERV表达。
结果
大多数差异表达的HERV在肿瘤组织中表达降低（166个下调，50个上调），这表明HERV表达模式在塑造HCC的病理生理格局中可能具有潜在的功能作用。具体而言，已知调节细胞分化的HERV-H家族成员的抑制可能导致肿瘤去分化、可塑性增加和转移潜能增强。这种分化控制的丧失和适应性增加可能在推动肝癌进展中起关键作用。
讨论
我们的研究突出了HERV表达与HCC之间的显著关联，强调了肿瘤组织中特定HERV家族的差异调节。例如，HERVH和ERVLE家族在肿瘤样本中表现出一致的下调，而HERVE和HERV9更常上调。这些变化可能反映了正常组织和恶性组织之间转录调控或染色质结构的潜在变化。观察到的数据表达模式可能反映了HERV与肿瘤生物学之间的多方面关系，而非表明单一的功能作用。需要进一步研究以确定这些表达差异是否促成肿瘤进展或由肿瘤进展导致，并探索它们作为生物标志物或治疗靶点的潜力。
临床试验编号
不适用。
Zotero 插件