Exosomal microRNA‐4661‐5p–based serum panel as a potential diagnostic biomarker for early‐stage hepatocellular carcinoma

Cho, Hyo Jung; Baek, Geum Ok; Seo, Chul Won; Ahn, Hye Shin; Sung, Suna; Son, Ju A; Kim, Soon Sun; Cho, Sung Won; Jang, Jeong Won; Nam, Suk Woo; Cheong, Jae Youn; Eun, Jung Woo

doi:10.1002/cam4.3230

Cited by 45 publications

(35 citation statements)

References 38 publications

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“…In particular, exo-miR-10b-5p appeared as a promising biomarker for early-stage HCC with an AUROC of 0.93, a sensitivity of 90.7% and specificity of 75.0% [ 35 ]. Another set of miRNAs, exo-miR-25-3p, exo-miR-1269a, exo-miR-4661-5p, and exo-miR-4746-5p with increased expression in HCC were found by selecting driver oncogenic miRNAs using analysis of miRNAs expression profiles from three different RNA sequencing datasets of human HCC [ 36 ]. In particular, serum exo-miR-4661-5p could detect HCC at all stages with AUROC of 0.92; even at early-stage HCC, the AUROC remained at 0.92.…”

Section: Microrna Biomarkersmentioning

confidence: 99%

“…Also, Table 1 , which summarizes a series of microRNAs that are not further discussed in the review, clearly shows that most studies that evaluate circulating miRNAs as potential biomarkers for HCC detection were conducted using Asian cohorts, which are generally characterized by a high-frequency of HBV-induced HCC, and no or small numbers of HCC induced by HCV, alcohol or NAFLD. In addition, these studies were conducted involving small groups of patients and have yet to be validated within large cohort of patients [ 35 , 36 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Microrna Biomarkersmentioning

confidence: 99%

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Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Debes

Romagnoli²,

Prieto³

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.

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Section: Microrna Biomarkersmentioning

confidence: 99%

Section: Microrna Biomarkersmentioning

confidence: 99%

Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Debes

Romagnoli²,

Prieto³

et al. 2021

Cancers

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“…Moreover, aberrantly regulated exo-miRs can promote HCC progression and metastasis by altering the genetic network [ 20 ]. An in vitro study by Lin et al, exosome-mediated miR delivery was shown to promote the EMT and metastasis in HCC [ 21 ]. However, few studies have investigated circulating exo-miR profiles as metastasis predictors or promoters in HCC.…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma

Eun

Seo

Baek

et al. 2020

Cancers

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Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group (p = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression (p < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial–mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.

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“…For the early detection of HCC, serum exo-miR-10b-5p has been reported to be a promising biomarker, with 90.7% sensitivity and 75.0% specificity at the cut-off value of 1.8-fold[ 40 ]. Notably, a novel panel comprising exo-miR-4661-5p and exomiR-4746-5p yielded a best fit AUC of 0.947 with a sensitivity of 75% and a specificity of 91.7% for early-stage HCC[ 41 ]. A separate study reported that the combination of exo-miR-122, exo-miR-148a, and AFP was able to distinguish early HCC from cirrhosis with an AUC of 0.931[ 42 ].…”

Section: Non-invasive Biomarkers For Early Diagnosis Of Hccmentioning

confidence: 99%

Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Guan

Wang

Liu

et al. 2021

WJGO

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.

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Exosomal microRNA‐4661‐5p–based serum panel as a potential diagnostic biomarker for early‐stage hepatocellular carcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 45 publications

References 38 publications

Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma

Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

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