Dataset Information

Identification of Three Circulating MicroRNAs in Plasma as Clinical Biomarkers for Breast Cancer Detection.

ABSTRACT: The diagnostic value of microRNAs (miRNAs) for breast cancer (BC) is largely unknown. Here, our research aim was to explore new circulating miRNAs for BC diagnosis. First, we identified 14 common differentially expressed miRNAs in tissues by TCGA_BRCA and GSE97811 datasets and preliminarily validated them in serum by the GSE73002 dataset. Furthermore, we examined three plasma miRNAs in BC patients (n = 108) and healthy subjects (n = 103) by RT−PCR, namely, hsa-miR-100-5p, hsa-miR-191-5p and hsa-miR-342-3p. The levels of these three miRNAs in BC patients were higher than those in healthy controls (p < 0.05). The ROC curve analysis revealed that these three miRNAs had high diagnostic efficacy for BC and early-stage BC. The combination of hsa-miR-100-5p and hsa-miR-191-5p was the optimal combination for the diagnosis of BC and early-stage BC. Additionally, hsa-miR-100-5p was correlated with stage I−II, T1 stage, N0 stage and Luminal A subtype (p < 0.05). Hsa-miR-191-5p and hsa-miR-342-3p were irrelevant to TNM stage, T stage, N stage and molecular subtypes. Meanwhile, the biological function analysis indicated that these three miRNAs are mainly involved in the calcium signaling pathway, MAPK signaling pathway and microRNAs in cancer. In conclusion, these three miRNAs demonstrate a positive effect on detection and discovery in BC.

SUBMITTER: Wang S

PROVIDER: S-EPMC9821655 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Identification of Three Circulating MicroRNAs in Plasma as Clinical Biomarkers for Breast Cancer Detection.

Wang Shuang S Li Lijuan L Yang Mengmeng M Wang Xiaoyan X Zhang Huan H Wu Nan N Jia Kaichao K Wang Junchao J Li Menghui M Wei Lijuan L Liu Juntian J

Journal of clinical medicine 20221231 1

The diagnostic value of microRNAs (miRNAs) for breast cancer (BC) is largely unknown. Here, our research aim was to explore new circulating miRNAs for BC diagnosis. First, we identified 14 common differentially expressed miRNAs in tissues by TCGA_BRCA and GSE97811 datasets and preliminarily validated them in serum by the GSE73002 dataset. Furthermore, we examined three plasma miRNAs in BC patients (n = 108) and healthy subjects (n = 103) by RT−PCR, namely, hsa-miR-100-5p, hsa-miR-191-5p and hsa- ...[more]

PMID: 36615122

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Project description:Early detection is crucial for achieving a reduction in breast cancer mortality. Analysis of circulating cell-free microRNAs present in the serum of cancer patients has emerged as a promising new noninvasive biomarker for early detection of tumors and for predicting their molecular classifications. The rationale for this study was to identify subtype-specific molecular profiles of cell-free microRNAs for early detection of breast cancer in serum. Fifty-four early-stage breast cancers with 27 age-matched controls were selected for circulating microRNAs evaluation in the serum. The 54 cases were molecularly classified (luminal A, luminal B, luminal B Her2 positive, Her-2, triple negative). NanoString platform was used for digital detection and quantitation of 800 tagged microRNA probes and comparing the overall differences in serum microRNA expression from breast cancer cases with controls. We identified the 42 most significant (P ≤ 0.05, 1.5-fold) differentially expressed circulating microRNAs in each molecular subtype for further study. Of these microRNAs, 19 were significantly differentially expressed in patients presenting with luminal A, eight in the luminal B, ten in luminal B HER 2 positive, and four in the HER2 enriched subtype. AUC is high with suitable sensitivity and specificity. For the triple negative subtype miR-25-3p had the best accuracy. Predictive analysis of the mRNA targets suggests they encode proteins involved in molecular pathways such as cell adhesion, migration, and proliferation. This study identified subtype-specific molecular profiles of cell-free microRNAs suitable for early detection of breast cancer selected by comparison to the microRNA profile in serum for female controls without apparent risk of breast cancer. This molecular profile should be validated using larger cohort studies to confirm the potential of these miRNA for future use as early detection biomarkers that could avoid unnecessary biopsy in patients with a suspicion of breast cancer.

Project description:Prostate Cancer (PCa) overdiagnosis and overtreatment, as a consequence of the limited specificity of current detection and prognostication methods, remains a major challenge in clinical practice. Therefore, development and validation of new molecular biomarkers amenable of detecting clinically significant disease is crucial. MicroRNAs (miRNA) deregulation is common in cancer, constituting potential non-invasive biomarkers for PCa detection and prognostication. Herein, we evaluated the screening and prognostic biomarker potential of two onco-microRNAs (miR-182-5p and miR-375-3p) in liquid biopsies (plasma) of PCa patients with clinically localized disease undergoing curative-intent treatment. A first cohort of 98 PCa and 15 normal prostates were used to assess PCa-specificity of miR-182-5p in tissues. A cohort composed of PCa 252 patients and 52 asymptomatic controls allowed for assessment of diagnostic and prognostic value in plasmas. After RNA extraction from tissue and plasma samples, cDNA synthesis specific for miRNAs was performed followed by measurement of miR-182-5p and miR-375-3p relative expression by RT-qPCR, using U6 snRNA gene as reference. MiR-182-5p was significantly overexpressed in PCa tissues (p < 0.0001) and in plasma of PCa patients (p = 0.0020), compared to respective controls. Moreover, miR-182-5p expression identified PCa with AUC = 0.81 (95% CI: 0.725-0.892, p = 0.0001) in tissue and with 77% specificity and 99% NPV (AUC = 0.64, 95% CI: 0.561-0.709, p = 0.0021) in plasma. Both circulating miR-182-5p and miR-375-3p levels associated with more advanced pathologic stage and the former was significantly higher in patients that developed metastasis (p = 0.0145). Indeed, at the time of diagnosis, circulating miR-375-3p levels predicted which patients would develop metastasis, with almost 50% sensitivity, 76% specificity, and a NPV of 89% (AUC = 0.62, 95% CI: 0.529-0.713, p = 0.0149). We conclude that these two circulating miRNAs might be clinical useful as non-invasive biomarkers for detection and prediction of metastasis development at the diagnosis together with clinical variables used in routine practice.

Project description:BackgroundBreast cancer (BC) is the most frequently diagnosed cancer among women. Numerous studies explored cell-free circulating microRNAs as diagnostic biomarkers of BC. As inconsistent and rarely intersecting microRNA panels have been reported thus far, we aim to evaluate the overall diagnostic performance as well as the sources of heterogeneity between studies.MethodsBased on the search of three online search engines performed up to March 21st 2022, 56 eligible publications that investigated diagnostic circulating microRNAs by utilizing Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) were obtained. Primary studies' potential for bias was evaluated with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). A bivariate generalized linear mixed-effects model was applied to obtain pooled sensitivity and specificity. A novel methodology was utilized in which the sample and study models' characteristics were analysed to determine the potential preference of studies for sensitivity or specificity.ResultsPooled sensitivity and specificity of 0.85 [0.81-0.88] and 0.83 [0.79-0.87] were obtained, respectively. Subgroup analysis showed a significantly better performance of multiple (sensitivity: 0.90 [0.86-0.93]; specificity: 0.86 [0.80-0.90]) vs single (sensitivity: 0.82 [0.77-0.86], specificity: 0.83 [0.78-0.87]) microRNA panels and a comparable pooled diagnostic performance between studies using serum (sensitivity: 0.87 [0.81-0.91]; specificity: 0.83 [0.78-0.87]) and plasma (sensitivity: 0.83 [0.77-0.87]; specificity: 0.85 [0.78-0.91]) as specimen type. In addition, based on bivariate and univariate analyses, miRNA(s) based on endogenous normalizers tend to have a higher diagnostic performance than miRNA(s) based on exogenous ones. Moreover, a slight tendency of studies to prefer specificity over sensitivity was observed.ConclusionsIn this study the diagnostic ability of circulating microRNAs to diagnose BC was reaffirmed. Nonetheless, some subgroup analyses showed between-study heterogeneity. Finally, lack of standardization and of result reproducibility remain the biggest issues regarding the diagnostic application of circulating cell-free microRNAs.

Dataset Information

Identification of Three Circulating MicroRNAs in Plasma as Clinical Biomarkers for Breast Cancer Detection.

Publications

Identification of Three Circulating MicroRNAs in Plasma as Clinical Biomarkers for Breast Cancer Detection.

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