Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Intercellular communication among cancer cells and their microenvironment is crucial to disease progression. Exosomes are extracellular vesicles secreted by multiple types of cells into the extracellular space, which contain a variety of active components of secretory cells, including lipids, proteins, RNA and DNA. This vesicle structure involves in the exchange of materials and information between cells and plays an important role in the development of many diseases. Studies have shown that exosomes participate in the communication between HCC cells and non-HCC cells and regulate the occurrence and development of hepatocellular carcinoma. Therefore, exosomes may be specific biomarkers for early diagnosis and metastasis of HCC, which are also potential targets for the treatment of HCC. This review summarizes the characteristic, types and biological functions of exosomes and discusses their research progress and application prospects in the diagnosis and treatment of HCC.
Background: Circulating exosomal microRNAs (miRNAs) are considered as potentially non-invasive biomarkers for early detection and prognosis of cancers. Due to the lack of highly sensitive and specific molecular markers, a lot of patients with hepatocellular carcinoma are diagnosed in advanced stages. This study aims to explore the expression mode and clinical detection value of serum exosomal miR-34a in HCC, providing new potential targets and theoretical basis for the early diagnosis and prognosis monitoring of hepatocellular carcinoma. Methods: The expression of serum exosomal miR-34a in 60 HCC patients before and after operation and 60 healthy examiners was abstracted and detected by ultracentrifugation and real-time quantitative PCR. Using ROC analysis, Kaplan-Meier survival analysis and Cox regression analysis, the value of serum exosomal miR-34a on diagnosis and prognosis in HCC patients was assessed.Results: The expression level of serum exosomal miR-34a in preoperative patients was reduced significantly comparing with that in healthy examiners and postoperative patients (P<0.01; P<0.05). Moreover, the decrease of serum exosomal miR-34a was correlated significantly with differentiation degree, TNM stage, tumor infiltration depth and lymph node metastasis(P<0.05), but had no statistical differences with gender, age, ALT, AST, viral infection, cirrhosis and tumor size of HCC patients (P>0.05). At the same time, the combination of serum exosomal miR-34a and α-fetoprotein (AFP) showed high capability on diagnosis to distinguish healthy examiners and HCC patients through ROC analysis. The overall survival of patients with lower expression of serum exosomal miR-34a was worse than that of patients with high level expression by Kaplan-Meier survival analysis (P<0.05). Univariate and multivariate Cox regression analysis both showed that serum exosomal miR-34a was independently related to OS. Conclusions: Collectively, serum exosomal miR-34a is significantly down-regulated in HCC patients and might be a novel noninvasive biomarker for diagnosis and prognosis of HCC.
Introduction Approximately half of patients with severe haemophilia A are caused by structural variants in the F8 gene. Unlike inversions or deletions directly impairing the integrity of F8, some duplications do not completely disrupt the open reading frame or even retain an intact F8 copy. Currently, only a few duplication breakpoints were precisely characterized, and the corresponding rearrangement mechanisms and clinical outcomes remain to be further investigated. Aim Establishing an effective strategy for breakpoint characterization of duplications and revealing their rearrangement mechanisms. Methods AccuCopy is used for the detection of duplications, long‐distance PCR for the characterization of tandem duplications, genome walking technique and whole genome sequencing for the characterization of inverted duplications. Results Four F8 duplication rearrangements were successfully characterized at the nucleotide level: one tandem duplication (exons 7–11) and three inverted duplications (exons 7–22, exons 2–26, and exons 15–22). Two shared features of inverted duplication were found after carefully analysing our results and breakpoint information in the literature: 1, an inverted fragment was inserted into the original chromosome via two junctions; 2, one junction is mediated by a pair of inverted repetitive elements, while the other consists of two breakpoints with microhomology. Conclusion Similar breakpoint features motivated us to propose a DNA replication‐based model to explain the formation of duplication rearrangements. Based on our model, we further divide the inverted duplications into three basic types: type I with a DEL‐NOR/INV‐DUP pattern, type II with a DUP‐NOR/INV‐DUP pattern and type III with a DUP‐TRP/INV‐DUP pattern.
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