Comparison of the Metastasis Predictive Potential of mRNA and Long Non-Coding RNA Profiling in Systemically Untreated Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tumor Biopsies
2.2. Microarray Analysis and Re-Annotation
2.3. Data Processing, Classification and Voting
2.4. Statistical Analysis
3. Results
3.1. Classification with ≥90% Sensitivity Threshold Followed by Voting
3.2. Classification with Balanced Accuracy Optimization Followed by Voting
3.3. Classification of ER Positive Breast Cancer Patients Followed by Voting
4. Discussion
4.1. Classification Using lncRNA Compared to mRNA Improved Prognostic Power
4.2. Classification Followed by Voting Supports lncRNAs as Better Prognostic Predictors
4.3. Comparison of the Two Voting Strategies for Clinical Signature Development
4.4. Comparison of the Two Voting Strategies for Clinical Application in ER Positive Patients
4.5. LncRNAs and Their Countless Roles
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Appendix Methods
Classification
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
Method | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
LDA | 98 | 16 | 57 | 95 | 31 | 63 | 0.22 |
R-SVM | 96 | 40 | 68 | 91 | 35 | 63 | 0.74 |
L-SVM | 91 | 42 | 66 | 91 | 38 | 65 | 0.51 |
RF | 91 | 31 | 61 | 93 | 44 | 68 | 0.17 |
NB | 91 | 35 | 63 | 93 | 36 | 65 | 0.43 |
COX-RS | 91 | 11 | 51 | 91 | 35 | 63 | 0.048 |
LR | 91 | 15 | 53 | 93 | 16 | 55 | 0.44 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
No. of Rec. Votes | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
≥1 | 100 | 0 | 50 | 100 | 2 | 51 | 0.49 |
≥2 | 100 | 2 | 51 | 100 | 9 | 55 | 0.32 |
≥3 | 98 | 13 | 55 | 98 | 18 | 58 | 0.38 |
≥4 | 98 | 18 | 58 | 98 | 33 | 65 | 0.18 |
≥5 | 96 | 38 | 67 | 95 | 44 | 69 | 0.43 |
≥6 | 87 | 49 | 68 | 87 | 60 | 74 | 0.20 |
7 | 69 | 69 | 69 | 71 | 73 | 72 | 0.37 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
Method | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
LDA | 62 | 62 | 62 | 56 | 65 | 61 | 0.51 |
R-SVM | 75 | 65 | 70 | 69 | 69 | 69 | 0.51 |
L-SVM | 67 | 71 | 69 | 60 | 73 | 66 | 0.63 |
RF | 67 | 64 | 65 | 65 | 67 | 66 | 0.49 |
NB | 62 | 76 | 69 | 62 | 71 | 66 | 0.63 |
COX-RS | 62 | 76 | 69 | 58 | 62 | 60 | 0.90 |
LR | 60 | 75 | 67 | 56 | 75 | 65 | 0.56 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
No. of Rec. Votes | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
≥1 | 85 | 45 | 65 | 91 | 36 | 64 | 0.51 |
≥2 | 84 | 53 | 68 | 85 | 56 | 71 | 0.37 |
≥3 | 75 | 67 | 71 | 76 | 62 | 69 | 0.57 |
≥4 | 65 | 71 | 68 | 64 | 73 | 68 | 0.50 |
≥5 | 60 | 78 | 69 | 53 | 80 | 66 | 0.63 |
≥6 | 56 | 85 | 71 | 36 | 85 | 61 | 0.92 |
7 | 27 | 95 | 61 | 22 | 89 | 55 | 0.78 |
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Characteristics | Recurrence Development | Recurrence-Free |
---|---|---|
No. of patients | 80 (50) | 80 (50) |
Age at diagnosis (range: 33–88 years) ≤50 years >50 years | 14 (8.8) 66 (41.3) | 10 (6.3) 70 (43.8) |
Tumor size | ||
<2 cm | 27 (16.9) | 30 (18.8) |
2–5 cm | 53 (33.1) | 49 (30.6) |
n/a | 1 (0.6) | |
Estrogen receptor status a | ||
Positive | 52 (32.5) | 50 (31.3) |
Negative | 22 (13.8) | 24 (15) |
n/a | 6 (3.8) | 6 (3.75) |
Tumor type | ||
Invasive ductal carcinoma (IDC) | 62 (38.8) | 65 (40.6) |
Invasive lobular carcinoma (ILC) | 9 (5.6) | 9 (5.6) |
Mucinous carcinoma | 2 (1.3) | 2 (1.3) |
Papillary carcinoma | 3 (1.9) | 2 (1.3) |
Carcinoma with metaplasia | 2 (1.3) | 2 (1.3) |
n/a | 2 (1.3) | - |
Histologic grade | ||
1 (good) | 12 (7.5) | 15 (9.4) |
2 (intermediate) | 28 (17.5) | 25 (15.6) |
3 (poor) | 22 (13.8) | 24 (15) |
n/a | 18 (11.3) | 16 (10) |
Median year of surgery (range 1980–2003) | 1993 | 1994 |
Mean time to recurrence (months) | 58.5 | n/a |
Mean follow-up (months) | 88.3 | 250.35 |
Alive at end of follow-up | 1 | 48 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
Method | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
LDA | 90 | 30 | 60 | 90 | 58 | 74 | 0.0055 |
R-SVM | 90 | 32 | 61 | 90 | 53 | 71 | 0.038 |
L-SVM | 91 | 32 | 62 | 90 | 50 | 70 | 0.082 |
RF | 91 | 40 | 66 | 90 | 52 | 71 | 0.20 |
NB | 91 | 31 | 61 | 91 | 38 | 64 | 0.33 |
COX-RS | 90 | 21 | 56 | 91 | 38 | 64 | 0.089 |
LR | 90 | 16 | 53 | 90 | 50 | 70 | 0.0013 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
No. of Rec. Votes | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
≥1 | 100 | 0 | 50 | 98 | 19 | 58 | 0.093 |
≥2 | 100 | 10 | 55 | 92 | 29 | 61 | 0.17 |
≥3 | 99 | 20 | 59 | 92 | 41 | 67 | 0.086 |
≥4 | 96 | 28 | 62 | 92 | 50 | 71 | 0.056 |
≥5 | 91 | 38 | 64 | 91 | 60 | 76 | 0.013 |
≥6 | 83 | 45 | 64 | 88 | 64 | 76 | 0.013 |
7 | 65 | 64 | 64 | 80 | 75 | 78 | 0.0042 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
Method | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
LDA | 68 | 60 | 64 | 75 | 74 | 74 | 0.035 |
R-SVM | 70 | 66 | 68 | 76 | 68 | 72 | 0.26 |
L-SVM | 72 | 61 | 67 | 72 | 71 | 72 | 0.20 |
RF | 71 | 65 | 68 | 75 | 71 | 73 | 0.20 |
NB | 75 | 65 | 70 | 69 | 71 | 70 | 0.50 |
COX-RS | 69 | 60 | 64 | 68 | 74 | 71 | 0.11 |
LR | 65 | 64 | 64 | 79 | 76 | 78 | 0.0042 |
mRNA | lncRNA | ||||||
---|---|---|---|---|---|---|---|
No. of Rec. Votes | Sensitivity | Specificity | Accuracy a | Sensitivity | Specificity | Accuracy a | pb |
≥1 | 92 | 29 | 61 | 88 | 51 | 69 | 0.083 |
≥2 | 82 | 46 | 64 | 84 | 59 | 71 | 0.11 |
≥3 | 78 | 62 | 70 | 80 | 65 | 73 | 0.32 |
≥4 | 69 | 66 | 68 | 75 | 72 | 74 | 0.14 |
≥5 | 62 | 74 | 68 | 70 | 76 | 73 | 0.20 |
≥6 | 53 | 85 | 69 | 65 | 88 | 76 | 0.10 |
7 | 38 | 95 | 66 | 53 | 94 | 73 | 0.11 |
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Do, T.T.N.; Block, I.; Burton, M.; Sørensen, K.P.; Larsen, M.J.; Bak, M.; Cold, S.; Thomassen, M.; Tan, Q.; Kruse, T.A. Comparison of the Metastasis Predictive Potential of mRNA and Long Non-Coding RNA Profiling in Systemically Untreated Breast Cancer. Cancers 2021, 13, 4907. https://doi.org/10.3390/cancers13194907
Do TTN, Block I, Burton M, Sørensen KP, Larsen MJ, Bak M, Cold S, Thomassen M, Tan Q, Kruse TA. Comparison of the Metastasis Predictive Potential of mRNA and Long Non-Coding RNA Profiling in Systemically Untreated Breast Cancer. Cancers. 2021; 13(19):4907. https://doi.org/10.3390/cancers13194907
Chicago/Turabian StyleDo, Thi T. N., Ines Block, Mark Burton, Kristina P. Sørensen, Martin J. Larsen, Martin Bak, Søren Cold, Mads Thomassen, Qihua Tan, and Torben A. Kruse. 2021. "Comparison of the Metastasis Predictive Potential of mRNA and Long Non-Coding RNA Profiling in Systemically Untreated Breast Cancer" Cancers 13, no. 19: 4907. https://doi.org/10.3390/cancers13194907