Dataset Information

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

ABSTRACT: In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.

SUBMITTER: Giussani M

PROVIDER: S-EPMC8391908 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

Giussani Marta M Ciniselli Chiara Maura CM De Cecco Loris L Lecchi Mara M Dugo Matteo M Gargiuli Chiara C Mariancini Andrea A Mancinelli Elisa E Cosentino Giulia G Veneroni Silvia S Paolini Biagio B Orlandi Rosaria R Gennaro Massimiliano M Iorio Marilena Valeria MV Depretto Catherine C Ferranti Claudio C Sozzi Gabriella G Sensi Marialuisa M Colombo Mario Paolo MP Scaperrotta Gianfranco G Tagliabue Elda E Verderio Paolo P

Cancers 20210810 16

In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) o ...[more]

PMID: 34439180

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Project description:Background: Cervical cancer is the most common malignant tumor in the female reproductive system, while the efficacy of routine screening strategy is unsatisfied. New molecular tests need to be developed. miRNAs participate in many pathologic processes, and circulating miRNAs are promising non-invasive biomarkers in tumors. Objectives: This study aimed to identify the circulating miRNAs associated with both cervical cancer and cervical intraepithelial neoplasia (CIN), and establish a non-invasive classifier for cervical lesions using circulating miRNAs. Methods: This study consisted of 5 steps: miRNAs screening, miRNAs validation, classifier establishment, independent validation and in silico analyses. Three cohorts were included in our study: In screening stage, 24 samples including 14 cases and 10 controls were retrieved; In validation stage, 380 samples including 200 cases and 180 controls were recruited; In independent validation stage, 47 samples comprising 26 cases and 21 controls were included. miRNAs were quantified by RT-qPCR. A classifier was built with random forest algorithm using validation samples and selected miRNAs, which were then validated in an independent cohort. To explore the function of selected miRNAs, in silico analyses were performed. Target genes of selected miRNAs were predicted by the overlap of three online tools. Enrichment analyses were executed with predicted target genes. Differential analysis of target genes was carried out with open access expression assay datasets of cervical tissues. Results: 6 miRNAs (hsa-miR-26b-5p, hsa-miR-146b-5p, hsa-miR-191-5p, hsa-miR-484, hsa-miR-574-3p, hsa-miR-625-3p) were screened out from 754 miRNAs. They were associated with cervical lesions and were selected to establish a classifier. The accuracy of the classifier were 0.7218 (0.7117, 0.7319) in validation samples, which was 0.7021 in the independent cohort. 958 target genes were predicted and enriched in 23 pathways (MAPK, human papillomavirus infection and Wnt signaling pathway, etc.). 55 genes were identified as the most likely target genes by differential analysis. Conclusion: The 6 circulating miRNAs were related to cervical lesions and could serve as non-invasive biomarkers.

Dataset Information

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

Publications

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

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