Dataset Information

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

ABSTRACT: Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early-stage HCC (single tumor < 2 cm). We aimed to investigate diagnostic serum exosomal microRNA (exo-miR) panel for early-stage HCC. Driver oncogenic miR (onco-miR) candidates were selected by integrative analysis of miR expression profiles from three different RNA sequencing datasets of human HCC. Expressions of selected onco-miRs in serum exosome were measured using quantitative real-time PCR. Diagnostic performances of serum exo-miRs for HCC were evaluated in the test cohort (N = 24) and validation cohort (N = 144). Serum exo-miR panels were developed using a logistic regression model, and their diagnostic performance was evaluated. Six promising driver onco-miRs, including miR-25-3p, miR-140-3p, miR-423-3p, miR-1269a, miR-4661-5p, and miR-4746-5p, were identified by integrative analysis of three different RNA sequencing datasets. Among the six candidates, four serum exo-miRs (miR-25-3p, miR-1269a, miR-4661-5p, and miR-4746-5p) showed promising performance in the test cohort with area under the receiving operator curve (AUROC) >0.8. In our validation study, serum exo-miR-4661-5p could diagnose HCC in all stages (AUROC = 0.917), even in early stage (AUROC = 0.923), with a greater accuracy than other candidate serum exo-miRs and serum AFP. The panel composed of exo-miR-4661-5p and exo-miR-4746-5p was identified as the most accurate biomarker for early-stage HCC (AUROC = 0.947, 95% confidence interval = 0.889-0.980, sensitivity = 81.8%, and specificity = 91.7%). In conclusion, exo-miR-4661-5p-based serum panel is a promising diagnostic marker for early-stage HCC.

SUBMITTER: Cho HJ

PROVIDER: S-EPMC7402848 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Cho Hyo Jung HJ Baek Geum Ok GO Seo Chul Won CW Ahn Hye Ri HR Sung Suna S Son Ju A JA Kim Soon Sun SS Cho Sung Won SW Jang Jeong Won JW Nam Suk Woo SW Cheong Jae Youn JY Eun Jung Woo JW

Cancer medicine 20200614 15

Currently, a reliable serum biomarker for hepatocellular carcinoma (HCC) has not been established, particularly for early-stage HCC (single tumor < 2 cm). We aimed to investigate diagnostic serum exosomal microRNA (exo-miR) panel for early-stage HCC. Driver oncogenic miR (onco-miR) candidates were selected by integrative analysis of miR expression profiles from three different RNA sequencing datasets of human HCC. Expressions of selected onco-miRs in serum exosome were measured using quantitativ ...[more]

PMID: 32537885

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Project description:BackgroundSmall cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis.MethodsTo investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs.ResultsFrom the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers.ConclusionOur study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

Dataset Information

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

Publications

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

Similar Datasets

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