Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Sohn W
PROVIDER: S-EPMC4650928 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancies. The diagnosis of HCC remains challenging due to the low sensitivity and specificity of the diagnostic method. Exosomes, which are abundant in various proteins from parent cells, play pivotal roles in intercellular communication and have been confirmed as promising sources of disease biomarkers. Herein, we performed a simple but robust proteomic profiling on exosomes derived from 1 μL of serum using a data-independent acquisition (DIA) method for the first time, to screen potential biomarkers for the diagnosis of HCC. Ten pivotal differentially expressed proteins (DEPs) (von Willebrand factor (VWF), LGALS3BP, TGFB1, SERPINC1, HPX, HP, HBA1, FGA, FGG, and FGB) were screened as a potential candidate biomarker panel, which could completely discriminate patients with HCC from normal control (NC). Interestingly, Gene Expression Profiling Interactive Analysis (GEPIA) revealed that the expression levels of four genes increased and those of six genes decreased in HCC tissues compared with normal tissues, which were in concordance with protein expression levels. In conclusion, we screened 10 exosomal proteins holding promise for acting as a potential candidate biomarker panel for detection of HCC through a simple but robust proteomic profiling.
| S-EPMC7808137 | biostudies-literature
Project description:Exosomal microRNAs have recently been studied as the potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and Western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 was further analyzed and significantly higher in HCC than LC and normal control (NC) groups (P < 0.001), but not different from chronic hepatitis group (P > 0.05). The receiver operating characteristic curve was used to evaluate the diagnostic performance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95% confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha-fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607-0.803). Binary logistic regression was adopted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a, and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggest that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.
| S-EPMC5943469 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with high mortality. Circulating miRNA has been demonstrated as a novel noninvasive biomarker for many tumors. This study aimed to investigate the potential of circulating miR-125b as a prognostic marker of HCC. Exosomes were extracted from serum samples collected from two independent cohorts: cohort 1: HCC (n=30), chronic hepatitis B (CHB, n=30), liver cirrhosis (LC, n=30); cohort 2: HCC (n=128). We found that miR-125b levels were remarkably increased in exosomes compared to those in serum from patients with CHB, LC, and HCC (P<0.01, respectively). However, miR-125b levels in exosomes and the serum from HCC patients were inferior to that of CHB (P<0.01 and P=0.06) and LC patients (P<0.01 for all). Additionally, miR-125b levels in exosomes were associated with tumor number (P=0.02), encapsulation (P<0.01), and TNM stage (P<0.01). Kaplan-Meier analysis indicated that HCC patients with lower exosomal miR-125b levels showed reduced time to recurrence (TTR) (P<0.01) and overall survival (OS) (P<0.01). Furthermore, multivariate analysis revealed that miR-125b level in exosomes, but not in serum, was an independent predictive factor for TTR (P<0.001) and OS (P=0.011). Exosomal miR-125b levels predicted the recurrence and survival of HCC patients with an area under the ROC curve of 0.739 (83.0% sensitivity and 67.9% specificity) and 0.702 (82.5% sensitivity and 53.4% specificity). In conclusion, exosomal miR-125b could serve as a promising prognostic marker for HCC.
| S-EPMC5546809 | biostudies-other
Project description:BackgroundA reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis.MethodsExosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs.ResultsA total of 24 miRNAs showed differential levels of enrichment with P < 0.05 and |log2 fold change| > 1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively.ConclusionOur results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.
| S-EPMC7008302 | biostudies-literature
Project description:DesignFrom July 2016 to June 2018, 36 women with symptomatic early pregnancy around 4-8 weeks of gestation were recruited into the study. Among them, there were 16 women with viable intrauterine pregnancy (VIP), 9 women with spontaneous abortion (SA), and 11 women of EP. Serum exosomal miRNAs were extracted and measured at the first prenatal visit. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP.ResultsConcentrations of miR-378d in serum exosomes were significantly higher in EP than in VIP and also SA group. As a single marker, miR-378d had the highest specificity of 64% at the sensitivity of 89.1%. Comparatively, both combined panels of hCG, progesterone, miR-100-5p and hCG, progesterone, and miR-215-5P yielded the specificity of 96%. Panels for all markers achieved the highest specificity of 80% at the sensitivity of 91%.ConclusionsAlthough further validation in large-scale prospective studies is necessary, our results suggest that serum exosomal miR-378d, miR-100-5p, and miR-215-5P are promising biomarkers for early EP.
| S-EPMC7305552 | biostudies-literature
Project description:Although Kawasaki disease is the main cause of acquired heart disease in children, no diagnostic biomarkers are available. We aimed to identify candidate biomarkers for diagnosing Kawasaki disease using serum exosomal microRNAs (miRNAs). Using frozen serum samples from a biobank, high-throughput microarray technologies, two-stage real-time quantitative PCR, and a self-referencing strategy for data normalization, we narrowed down the list of biomarker candidates to a set of 4 miRNAs. We further validated the diagnostic capabilities of the identified miRNAs (namely, CT(miR-1246)-CT(miR-4436b-5p) and CT(miR-197-3p)-CT(miR-671-5p)) in 79 samples from two hospitals. We found that this 4-miRNA set could distinguish KD patients from other febrile patients as well as from healthy individuals in a single pass, with a minimal rate of false positives and negatives. We thus propose, for the first time, that serum exosomal miRNAs represent candidate diagnostic biomarkers for Kawasaki disease. Additionally, we describe an effective strategy of screening for biomarkers of complex diseases even when little mechanistic knowledge is available.
| S-EPMC5357789 | biostudies-literature
Project description:BackgroundSerum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy.MethodsPatients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value.Results30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, - 122-3p, and - 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, - 122-3p, - 486-3p, -451a, - 122-5p, - 3591-3p, - 486-5p, -151a-3p, -92a-3p, -320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, -151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52-0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, -451a, -151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation.ConclusionThese results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis.Trial registrationChinese Clinical Trial Registy ( ChiCTR-IOR-16008027 , Date of Registration:2016-03-01).
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Project description:Long noncoding RNAs (lncRNAs), such as LINC00462, HOTAIR, and MALAT1, are significantly upregulated in hepatocellular carcinoma (HCC) tissues. However, lncRNA expression in the serum of HCC patients is still unclear. To identify candidate lncRNAs for HCC diagnosis, we purified exosomal total RNA from the serum of healthy volunteers (controls) and hepatitis, cirrhosis, and HCC patients. To assess the function of lncRNAs, small interfering RNAs and overexpression vectors were designed and cell viability and cell apoptosis assays conducted. The exosomes of the control group had a larger number of lncRNAs with a high amount of alternative splicing compared to hepatic disease patients. qPCR assays showed that lnc-FAM72D-3, lnc-GPR89B-15, lncZEB2-19, and lnc-EPC1-4 are differentially expressed in HCC. Furthermore, the expression level of lnc-EPC1-4 correlated with age. While the expression levels of lnc-GPR89B-15 and lnc-EPC1-4 correlated with serum alpha-fetoprotein level. lnc-FAM72D-3 knockdown decreased cell viability and promoted cell apoptosis, indicating that lnc-FAM72D-3 functions as an oncogene in HCC. In contrast, lnc-EPC1-4 overexpression inhibited cell proliferation and induced cell apoptosis, indicating that it functions as a tumor suppressor gene. Collectively, these findings show that lnc-FAM72D-3 and lnc-EPC1-4 play a novel role that might contribute to hepatocarcinogenesis and identify potential candidate biomarkers for HCC diagnosis.
| S-EPMC7343450 | biostudies-literature
Project description:Exosomal miRNAs are emerging as mediators of the interaction between mast cells (MCs) and tumor cells. The exosomal miRNAs can be internalized by liver cancer cells to inhibit cell metastasis. We explored the interaction between MCs and hepatocellular carcinoma (HCC) cells. We used hepatitis C virus E2 envelope glycoprotein (HCV-E2) to stimulate MCs and harvest MCs-derived exosomes to detect the miRNAs and changes of exosomal miRNAs before and after stimulation. Through miRNA microarray analysis, we identified 19 differentially expressed miRNAs in exosomes derived from MCs with or without HCV-E2 treatment. HCV-E2 not only increased the level of miRNA-490 in MCs and their secreted exosomes but also increased the levels of miRNA-490 in recipient HepG2 cells, which ultimately inhibited the ERK1/2 pathway. The transfection of antagomiR-490 significantly decreased the levels of miR-490 in MCs, MCs-derived exosomes, and recipient HepG2 cells and increased migration of HepG2, indicating that miR-490 is involved in the regulation of HepG2 cell migration. The present study suggests that MCs can inhibit HCC cell metastasis by inhibiting the ERK1/2 pathway by transferring the exosomal shuttle microRNAs into HCC cells, which provides new insights for the biological therapy of HCC induced by hepatitis C.
| S-EPMC5530191 | biostudies-other
Project description:Serum levels of liver enzymes, such as alanine transaminase, aspartate transaminase, and ?-fetoprotein, provide insight into liver function and are used during treatment of liver disease, but such information is limited. In the case of hepatocellular carcinoma (HCC), which is often not detected until an advanced stage, more sensitive biomarkers may help to achieve earlier detection. Serum also contains microRNAs, a class of small non-coding RNAs that play an important role in regulating gene expression. miR-122 is specific to the liver and correlates strongly with liver enzyme levels and necroinflammatory activity, and other microRNAs are correlated with the degree of fibrosis. miR-122 has also been found to be required for hepatitis C virus (HCV) infection, whereas other microRNAs have been shown to play antiviral roles. miR-125a-5p and miR-1231 have been shown to directly target hepatitis B virus (HBV) transcripts, and others are up- or down-regulated in infected individuals. MicroRNA profiles also differ in the case of HBV and HCV infection as well as between HBeAg-positive and negative patients, and in patients with occult versus active HBV infection. In such patients, monitoring of changes in microRNA profiles might provide earlier warning of neoplastic changes preceding HCC.
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