4.6 Article

Serum exosomal miR-34a as a potential biomarker for the diagnosis and prognostic of hepatocellular carcinoma

期刊

JOURNAL OF CANCER
卷 13, 期 5, 页码 1410-1417

出版社

IVYSPRING INT PUBL
DOI: 10.7150/jca.57205

关键词

hepatocellular carcinoma; exosome; miR-34a; molecular biomarker; diagnosis; prognosis

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资金

  1. Shanghai Sailing Program [19YF1405500]
  2. National Natural Science Foundation of China [82102491, 81772673]
  3. Initial Scientific Research Fund of Huashan Hospital Affiliated to Fudan University [2019QD003, 2018QD079]
  4. National Key Research and Development Plan of China [2018YFC2000200]

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This study found that serum exosomal miR-34a is significantly down-regulated in patients with hepatocellular carcinoma (HCC), and it may serve as a novel non-invasive biomarker for the diagnosis and prognosis 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 alpha-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.

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