Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis

Qu, Zhen; Wu, Junhua; Ji, Anlai; Qiang, Guanghui; Jiang, Yong; Jiang, Chunping; Ding, Yitao

doi:10.18632/oncotarget.20881

Cited by 96 publications

(79 citation statements)

References 40 publications

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“…Recent publications have shown that some miRNAs offer good diagnostic efficacy for HCC. Table S2 included miR‐24, miR‐665, miR‐150, and miR‐296, which have been reported as upregulated in serum from individuals with HCC . However, miR‐122 and miR‐21, which were upregulated in serum from patients with HCC in many reports, were not significantly different between HCC and NC.…”

Section: Discussionmentioning

confidence: 99%

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Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Chuma

Toyoda

Matsuzaki³

et al. 2019

Hepatology Research

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Aims Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real‐time quantitative reverse transcription–polymerase chain reaction (PCR). Results Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA‐1246 (miR‐1246). Quantitative PCR confirmed that miR‐1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR‐1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR‐1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR‐1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion Circulating miR‐1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

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Section: Discussionmentioning

confidence: 99%

“…Some upregulated miRNAs had previously been reported as correlating with poor prognosis and metastasis in several types of cancers. For example, miR‐658 with gastric cancers, miR‐4286 with esophageal adenocarcinomas, miR‐486‐3p with bladder cancer, miR‐1260a with breast cancers, and, above all, miR‐665 with HCC …”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Chuma

Toyoda

Matsuzaki³

et al. 2019

Hepatology Research

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“…Serum exosomal miR-665 levels were significantly higher in HCC patients than those in healthy subjects. 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] .…”

Section: Exosomal Rna Biomarkersmentioning

confidence: 97%

“…For instance, HCC cell-derived exosomes have been shown to activate the MAPK/ERK pathway through miR-665 and further promote the proliferation of tumour cells [40] . Whereas, the expression of miR-320a was significantly downregulated in HCC cell lines.…”

Section: Modulation Of Hcc Tumour Growth and Metastasismentioning

confidence: 99%

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

Jayachandran¹,

Manda²,

Shrestha³

et al. 2018

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Hepatocellular carcinoma (HCC) commonly presents at an advanced stage due to the lack of efficient early screening tools. Early, non-invasive biomarkers useful in the diagnosis and prognosis of HCC would be of significant benefit for HCC management. Development of exosome-based liquid biopsy as a non-invasive method for the management of HCC has gained much traction. Exosomes are small membranous vesicles secreted by most cell types including HCC cells. Exosomes serve as couriers for the intercellular transfer of important biomolecules, including, protein, nucleic acids and lipids to nearby and distant cells in the body. The molecular cargos carried by exosome have been described to play significant roles in cancer progression. Herein, we will dissect how HCC-derived exosomes confer aggressive traits such as tumour growth, invasion, immune remodelling and drug resistance to HCC cells. We review the current literature concerning exosomes as biomarkers in a diagnostic setting, evaluating their prognostic, predictive and monitoring capabilities. This review will highlight and discuss emerging research in the utility of exosome-based liquid biopsies therapeutic tools in HCC management. Here we will also focus on advances in exosome biology in preclinical studies.

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“…. It has been shown that deregulation of miRNAs is associated with initiation and progression of various diseases, such as stroke, diabetes, cardiovascular diseases, and cancer (Banikazemi et al, 2018;Golabchi et al, 2018;Hoseini et al, 2018;Masoudi, Mehrabian, & Mirzaei, 2018;Mirzaei, 2017;Mirzaei, Ferns, Avan, & Mobarhan, 2017;Noruzi et al, 2018;Rabieian et al, 2018;Rashidi, Hoseini, Sahebkar, & Mirzaei, 2017;Rashidi, Malekzadeh, Goodarzi, Masoudifar, & Mirzaei, 2017;Saeedi Borujeni et al, 2018). Hence, it seems that miRNAs could be used as prognostic, diagnostic, and therapeutic biomarkers for monitoring various diseases (Fathullahzadeh et al, 2016;Gholamin et al, 2016;Huan et al, 2013;Jafari et al, 2018;Jamali et al, 2018;Keshavarzi, Darijani, et al, 2017;Keshavarzi, Sorayayi, et al, 2017;Khanmohammadi, Mir, Baniebrahimi, & Mirzaei, 2018;Mashreghi et al, 2018;Mirzaei, Sahebkar, Jaafari, Goodarzi, & Mirzaei, 2017;Saadatpour et al, 2016;Simonian, Mosallayi, & Mirzaei, 2018;Tavakolizadeh et al, 2018).…”

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confidence: 99%

microRNAs: Key players in virus‐associated hepatocellular carcinoma

Nahand

Bokharaei‐Salim

Salmaninejad

et al. 2018

Journal Cellular Physiology

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Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR‐222, miR‐25, miR‐92a, miR‐1, let‐7f, and miR‐21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV‐ and HBV‐related miRNAs which led to HCC progression.

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Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis

Cited by 96 publications

References 40 publications

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Circulating microRNA‐1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Exosome-based liquid biopsy in the management of hepatocellular carcinoma

microRNAs: Key players in virus‐associated hepatocellular carcinoma

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