Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study
Abstract
:1. Introduction
2. Results
2.1. Identification and Validation of a Plasma miRNA Signature for Breast Cancer Detection
2.2. Diagnostic miRNA Signature-Based Model Compared with Established BC Markers
2.3. Co-Expression Analysis of Circulating miR-125b-5p, miR-143-3p and miR-145-5p and Their Association with Immunohistochemical Markers of BC
2.4. Correlation Analysis of Circulating miR-125b-5p, miR-143-3p and miR-145-5p with Quantitative Imaging Parameters of Tumour Lesions
2.5. In Silico Studies
2.6. Cellular Origin of miR-125b-5p, miR-143-3p and miR-145-5p in Normal and BC Tissues
2.7. Combining Diagnostic test Results to Increase Accuracy
3. Discussion
4. Materials and Methods
4.1. Participants and Study Design
4.2. PET/MR Data Acquisition
4.3. Data Processing and Multiparametric Analysis
4.4. Plasma Sampling, RNA Extraction and Reverse Transcription
4.5. miRNA Microarray and Validation by Real-Time PCR (qRT-PCR)
4.6. TCGA Data Processing
4.7. In Situ Hybridization
4.8. Measurement of CA 15-3
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Healthy Control Samples (n = 78) | |
Age range | 28–84 years |
Mean ± S.D. | 51.05 ± 11.26 |
Breast Cancer Samples (n = 77) | |
Age range | 28–82 years |
Mean ± S.D. | 53.68 ± 12.02 |
Subtype | |
Luminal A | 16 |
Luminal B | 50 |
HER2+ | 7 |
Triple negative | 4 |
Ki67 | |
Low (1–20%) | 21 |
High (21–100%) | 56 |
Grade | |
G1 | 1 |
G2 | 41 |
G3 | 35 |
Stage | |
Stage I | 1 |
Stage II | 12 |
Stage III | 42 |
Stage IV | 22 |
Circulating Biomarkers | Estimate | Std. Error | p-Value |
---|---|---|---|
miR-125b-5p * | 9.018 | 2.401 | 0.000248 |
miR-143-3p * | 1.017 × 101 | 2.644 | 0.000179 |
CA15-3 * | 2.123 × 10−3 | 8.984 × 10−4 | 0.01941 |
CEA | 4.866 × 10−3 | 7.095 × 10−3 | 0.4939 |
miR-125b-5p | Disease + | Disease − | Total | Sensitivity | Specificity | Diagnostic Accuracy |
Test + | 61 (TP) | 16 (FP) | 77 | 0.79 (CI 0.68–0.88) | 0.79 (CI 0.69–0.88) | 0.79 (CI 0.72–0.85) |
Test − | 16 (FN) | 62 (TN) | 78 | |||
Total | 77 | 78 | 155 | |||
miR-143-3p | Disease + | Disease − | Total | Sensitivity | Specificity | Diagnostic accuracy |
Test + | 53 (TP) | 20 (FP) | 73 | 0.69 (CI 0.57–0.79) | 0.74 (CI 0.63–0.84) | 0.72 (CI 0.64–0.79) |
Test − | 24 (FN) | 58 (TN) | 82 | |||
Total | 77 | 78 | 155 | |||
CA15-3 | Disease + | Disease − | Total | Sensitivity | Specificity | Diagnostic accuracy |
Test + | 29 (TP) | 1 (FP) | 30 | 0.38 (CI 0.27–0.50) | 0.99 (CI 0.93–1.00) | 0.68 (CI 0.60–0.76) |
Test − | 47 (FN) | 75 (TN) | 122 | |||
Total | 76 | 76 | 152 | |||
CEA | Disease + | Disease − | Total | Sensitivity | Specificity | Diagnostic accuracy |
Test + | 25 (TP) | 8 (FP) | 73 | 0.33 (CI 0.23–0.45) | 0.89 (CI 0.80–0.95) | 0.61 (CI 0.53–0.69) |
Test − | 51 (FN) | 68 (TN) | 82 | |||
Total | 76 | 76 | 152 |
Stage II | Stage III | Stage IV | ||||||
---|---|---|---|---|---|---|---|---|
iAUCmean | Ki67 | Kepmean | SUVmax | iAUCmean | Ki67 | Ki67 | Ktransmean | |
miR-125-5p | ns | ns | ns | ns | ns | ns | −0.513 p-value 0.029 | −0.421 p-value 0.040 |
miR-143-3p | 0.943 p-value 0.005 | ns | 0.943 p-value 0.005 | 0.829 p-value 0.042 | 0.938 p-value 0.044 | ns | ns | ns |
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Share and Cite
Incoronato, M.; Grimaldi, A.M.; Mirabelli, P.; Cavaliere, C.; Parente, C.A.; Franzese, M.; Staibano, S.; Ilardi, G.; Russo, D.; Soricelli, A.; et al. Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study. Cancers 2019, 11, 876. https://doi.org/10.3390/cancers11060876
Incoronato M, Grimaldi AM, Mirabelli P, Cavaliere C, Parente CA, Franzese M, Staibano S, Ilardi G, Russo D, Soricelli A, et al. Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study. Cancers. 2019; 11(6):876. https://doi.org/10.3390/cancers11060876
Chicago/Turabian StyleIncoronato, Mariarosaria, Anna Maria Grimaldi, Peppino Mirabelli, Carlo Cavaliere, Chiara Anna Parente, Monica Franzese, Stefania Staibano, Gennaro Ilardi, Daniela Russo, Andrea Soricelli, and et al. 2019. "Circulating miRNAs in Untreated Breast Cancer: An Exploratory Multimodality Morpho-Functional Study" Cancers 11, no. 6: 876. https://doi.org/10.3390/cancers11060876