Decreased levels of serum exosomal miR‐638 predict poor prognosis in hepatocellular carcinoma

Abstract

Currently available studies have implicated that exosome-delivered microRNAs (miRNAs) play crucial roles in human cancer. However, the association of serum exosomal miR-638 and hepatocellular carcinoma (HCC) remains largely unknown. We aim to investigate the expression of exosomal miR-638 in serum of HCC patients and its prognostic role in this deadly disease. Kaplan-Meier and Cox regression analyses were used to determine the survival of patients histologically diagnosed with HCC. Reduced levels of exosomal miR-638 in serum samples from patients with HCC were identified by real-time PCR. Negative association of serum exosomal miR-638 with tumor size, vascular infiltration, and TNM stage was observed in HCC patients. Besides, the proliferation of Huh7 and SMCC7721 HCC cells were significantly inhibited when miR-638 was over-expressed in these cells. In addition, HCC patients with lower levels of serum exosomal miR-638 had poor overall survival than those with higher levels of exosomal miR-638 in serum. Our study strongly suggests that serum exosome-delivered miR-638 may serve as a novel circulating biomarker for HCC. Downregulation of miR-638 predicts poor prognosis for patients with HCC.

Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma

“…MiR-16 levels were used for normalization based on previously published results. 15,19 We found that the levels of exosomal miR-122, miR-125b, miR-145, miR-192, miR-194, miR-29a, miR-17-5p, and miR-106a were significantly upregulated in HCC patient serum. In addition, these exosomal miRNAs except miR-145 yielded AUC of 0.650 to 0.850 for discriminating HCC from healthy subjects ( Figure 2).…”

“…We first assessed the exosomes isolated from the serum. Transmission electron microscopy revealed spherical vesicles approximately 40 to 100 nm in diameter of all samples (Figure S1A), which is consistent with previous description of exosomes . We also performed Western blot analysis to detect 2 commonly used exosomal protein markers, namely, CD9 and CD63.…”

“…Transmission electron microscopy revealed spherical vesicles approximately 40 to 100 nm in diameter of all samples ( Figure S1A), which is consistent with previous description of exosomes. 15 We also performed Western blot analysis to detect 2 commonly used exosomal protein markers, namely, CD9 and CD63. With an equal amount of proteins loaded on each lane, the 2 exosome protein markers were highly enriched in the isolated exosomes relative to the serum ( Figure S1B).…”

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

“…Additionally, exosomal miR-665 levels were elevated in larger tumours with local invasion Serum extracellular vesicles [30] and at an advanced clinical stage (stage III/IV) of HCC [40] . Another study found decreased expression of serum exosomal miR-638 in HCC patients [41] . High miR-1247-3p in serum exosomal levels correlated with lung metastasis, poor overall survival and poor disease-free survival in HCC patients [19] .…”

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence

“…43 Furthermore, there are several studies regarding the diagnostic potential of circulating exosomal microRNAs in HCC including miR-21, 44 miR-125b,45 and miR-638 46. Furthermore, we need to explore the therapeutic potential of miR-92b targeted therapy for future preclinical and clinical applications.In addition to the functional analysis of exosomal miR-92b in tumor cell biology and tumor immunity, we have clarified the beneficial impact of circulating exosomal miR-92b for early prediction of posttransplant HCC recurrence (Figures 5 and 6).…”