Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma

Tomimaru, Yoshito; Eguchi, Hidetoshi; Nagano, Hiroaki; Wada, Hiroshi; Kobayashi, Shogo; Marubashi, Shigeru; Tanemura, Masahiro; Tomokuni, Akira; Takemasa, Ichiro; Umeshita, Koji; Kanto, Tatsuya; Doki, Yuichiro; Mori, Masaki

doi:10.1016/j.jhep.2011.04.026

Cited by 321 publications

(254 citation statements)

References 48 publications

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“…microRNAs (miRNAs) constitute a class of small non-coding RNAs that function as a novel class of global, post-transcriptional gene regulators by binding to partially complementary sequences in the 3' untranslated regions of downstream target mRNAs (9)(10)(11). Studies have indicated that miRNAs determine cancer metastasis and recurrence through regulating multiple target genes in numerous types of cancer, including HCC (12)(13)(14)(15). Furthermore, our recent study showed that miRNA profiles in DTCs in BM differ significantly between colorectal cancer patients with and without metastasis and that the expression level of specific miRNAs correlates significantly with malignant potential and long-term prognosis (16).…”

Section: Introductionmentioning

confidence: 99%

miR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma

Mukai

Tomimaru

Nagano

et al. 2015

Molecular and Clinical Oncology

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Abstract. The significance of disseminated tumor cells (DTCs) in bone marrow (BM) on tumor recurrence has not been investigated in patients with hepatocellular carcinoma (HCC). The aim of the present study was to clarify the molecular characteristics of DTCs that affect postoperative recurrence based on microRNA (miRNA) expression profiles in clinical HCC patients undergoing curative resection. DTCs were prospectively collected from the BM of preoperative HCC patients using immunomagnetic beads and subjected to miRNA microarray analysis. Microarray analysis of nine HCC patients (n=5 patients with postoperative HCC recurrence, n=4 patients without HCC recurrence) demonstrated that miR-615-3p is significantly upregulated in the DTCs of patients with recurrence compared to the DTCs from patients without recurrence. In vitro experiments demonstrated that the miR-615-3p expression level is significantly correlated with malignant characteristics in HCC cells. These data suggest that miR-615-3p in DTCs may play an important role in postoperative HCC recurrence, which suggests that miR-615-3p is a potential target molecule for regulating postoperative HCC recurrence.

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Section: Introductionmentioning

confidence: 99%

miR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma

Mukai

Tomimaru

Nagano

et al. 2015

Molecular and Clinical Oncology

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“…1). The diagnostic potential based on the changed specific circulating miRNA concentrations has been demonstrated by several independent studies, including miR-122-5p, -130-3p, and -223-3p in serum and miR-21-5p, -122-5p, and -223-3p in plasma (36 ). However, some of the circulating miRNAs identified showed inconsistent changes in different studies.…”

Section: Hepatocellular Carcinomamentioning

confidence: 95%

Current State of Circulating MicroRNAs as Cancer Biomarkers

et al. 2015

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BACKGROUND:Numerous studies have demonstrated the existence of stable regulatory RNAs, microRNAs (miRNAs), in the circulation and have shown that the spectrum of these extracellular miRNAs is affected by various pathologic conditions including cancers.CONTENT: Circulating miRNAs have been the focus of numerous cancer biomarker discovery efforts over the past few years; however, a considerable number of these studies have yielded inconsistent and irreproducible findings. Here, we have summarized and compared the results of studies covering 8 different cancer types to address key questions, including the possibility of using circulating miRNA to detect cancers and what factors may affect miRNA signatures. Although identifying circulating miRNA signatures to detect specific types of early stage cancers can be challenging, study results suggest that it may be possible to use miRNAs to detect cancers in general.

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“…Finally, 10 studies were included, with Tomimaru et al (2010) and Yu (2012) each counted as two studies because they analyzed the diagnosis as well as the prognosis for miR-21. Of these, five studies were enrolled into the diagnostic meta-analysis (Mizuguchi et al, 2011;Xu et al, 2011;Tomimaru et al, 2012;Yu, 2012;Chen et al, 2014) and seven studies (Tomimaru et al, 2010;Tomimaru et al, 2012;Yu, 2012;Gyöngyösi et al, 2014;Liu et al, 2014;Wang et al, 2014a,b) were included in the prognostic analysis.…”

Section: Literature Searchmentioning

confidence: 99%

“…The seven studies eligible for prognostic analysis were published from 2010 to 2014 and included a total of 723 patients; four studies were performed in China (Yu, 2012;Liu et al, 2014;Wang et al, 2014a,b), one in Hungary (Gyöngyösi et al, 2012), one in Japan (Tomimaru et al, 2012), and one in the United Kingdom (Tomimaru et al, 2010). The types of specimen included tissues (N = 4) and serum (N = 3).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…miRNAs have been proposed to represent ideal biomarker candidates because of their resistance to endogenous RNase resistance and high stability under different storage conditions (Schwarzenbach et al, 2014) and in the peripheral blood (Zhu et al, 2012;Wang et al, 2014c). Abnormal miRNA expression is closely associated with HCC (Tomimaru et al, 2012). Therefore, together with the benefits of their size, abundance, tissue specificity, and relative stability in circulation, miRNAs hold promise as unique accessible biomarkers with potentially important application value for early diagnosis, therapeutic effect monitoring, and the clinical assessment of prognosis in HCC .…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the value of miR-21 in the diagnosis of early stage HCC and its prognosis: a meta-analysis

Yan

Liu

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The diagnostic and prognostic value of miR-21 has been examined for hepatocellular carcinoma (HCC), with inconsistent results. Present meta-analysis summarized the diagnostic accuracy and the predictive role for survival of miR-21 in patients with HCC. All eligible studies were searched using PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases up to October 2014. For the diagnostic meta-analysis, the indices of miR-21 in the diagnosis of HCC were pooled using bivariate random-effect approach models. For the prognostic meta-analysis, data were synthesized with a random effect model, and the hazard ratio (HR) or odd ratio (OR) with its 95% confidence interval (95%CI) was used as the effect size estimate. Ten studies dealing with HCC were included. The overall pooled results for sensitivity, specificity, and the area under the curve (AUC) for the diagnostic meta-analysis (five studies) were 74. The combined data for the prognostic meta-analysis (seven studies) suggested that miR-21 overexpression in HCC correlated with poor overall survival [HR = 1.19 (95%CI = 0.44-1.94)], and higher miR-21 expression was associated with tumor, node, metastases (TNM) stage [OR = 0.34 (95%CI = 0.13-0.91)]. We concluded that miR-21 might be complementary to alpha fetal protein in HCC diagnosis, and might serve as an attractive estimator of HCC. We also demonstrated that miR-21 overexpression was associated with HCC TNM stage and with poor survival. As our study was limited, additional prospective studies are needed to validate these results.

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Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma

Cited by 321 publications

References 48 publications

miR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma

miR-615-3p expression level in bone marrow is associated with tumor recurrence in hepatocellular carcinoma

Current State of Circulating MicroRNAs as Cancer Biomarkers

Investigation of the value of miR-21 in the diagnosis of early stage HCC and its prognosis: a meta-analysis

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