Association of microRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Tissue Samples
2.2. RNA and DNA Extraction
2.3. BRAFV600E Mutation Analysis
2.4. qRT-PCR for miRNA Measurement
2.5. Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. miRNA Expression Levels in PTC and Their Association With PTC Recurrence
3.3. Detection of BRAFV600E Mutation in PTC Recurrence and Non-Recurrence Groups and Its Association With miRNA Expression
3.4. Association of miRNAs Expression and BRAFV600E Mutation with Clinicopathologic Features of PTC
3.5. Influence of Clinicopathological Features and miRNA Expression on Disease-Free Survival (DFS)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | All Patients (n = 400) | Non-Recurrence Group (n = 313) | Recurrence Group (n = 87) | p |
---|---|---|---|---|
Sex, n (%) Male Female | 53 (13.3) 347 (86.7) | 33 (10.6) 280 (89.4) | 20 (23.0) 67 (77.0) | 0.003 |
Age at initial surgery (years) Median (min-max) <45 years, n (%) ≥45 years, n (%) | 50 (18-83) 131 (32.8) 269 (67.2) | 53 (18-83) 91 (28.8) 222 (71.2) | 47 (18-75) 41 (47.1) 46 (52.9) | <0.001 0.001 |
Tumor size *, n (%) pT1a pT1b pT2 pT3 pT4 | 109 (27.3) 81 (20.3) 23 (5.8) 172 (43.0) 15 (3.8) | 97 (30.8) 64 (20.5) 18 (5.8) 128 (41.0) 6 (1.9) | 12 (13.8) 17 (19.5) 5 (5.7) 44 (50.6) 9 (10.3) | <0.001 <0.001 0.007 <0.001 0.439 |
Lymph node metastases at initial surgery, n (%) | 91 (22.8) | 48 (15.4) | 43 (49.4) | <0.001 |
Variable | OR (95% CI) | p-Value |
---|---|---|
Tumor size (T1 vs. T2–4) | 1.17 (0.56–2.44) | 0.680 |
Lymph nodes (pos vs. neg) | 3.66 (1.59–8.45) | 0.002 |
BRAFV600E (pos vs. neg) | 1.01 (0.45–2.11) | 0.994 |
miR- 146b | 1.09 (0.93–1.27) | 0.279 |
miR-222 | 1.21 (0.87–1.68) | 0.248 |
miR-21 | 1.50 (1.12–2.00) | 0.006 |
miR-221 | 0.86 (0.48–1.54) | 0.862 |
miR-181b | 1.08 (0.81–1.43) | 0.618 |
Univariate Analysis DFS | ||
HR (95% CI) | p-Value | |
Gender (female vs. male) | 0.47 (0.29-0.78) | 0.003 |
Age (<45 years vs. ≥45 years) | 1.77 (1.16-2.7) | 0.008 |
Tumor size (T1 vs. T2-4) | 0.52 (0.33-0.83) | 0.004 |
Lymph nodes (pos vs. neg) | 4.24 (2.78-6.47) | <0.001 |
BRAFV600E (pos vs. neg) | 1.01 (0.62-1.64) | 0.964 |
miR-146b (high vs. low) | 2.62 (1.65-4.15) | <0.001 |
miR-222 (high vs. low) | 2.39 (1.52-3.77) | <0.001 |
miR-21 (high vs. low) | 6.45 (3.63-11.44) | <0.001 |
miR-221 (high vs. low) | 1.82 (1.76-2.79) | 0.007 |
miR-181b (high vs. low) | 3.15 (1.93-5.15) | <0.001 |
Multivariate Analysis DFS | ||
HR (95% CI) | p-Value | |
Gender (female vs. male) | 0.85 (0.46-1.56) | 0.603 |
Age (<45 years vs. ≥45 years) | 1.37 (0.83-2.26) | 0.214 |
Tumor size (T1 vs. T2-4) | 1.19 (0.7-2.04) | 0.523 |
Lymph nodes (pos vs. neg) | 1.94 (1.12-3.36) | 0.017 |
BRAFV600E (pos vs. neg) | 0.8 (0.47-1.36) | 0.410 |
miR-146b (high vs. low) | 1.49 (0.77-2.89) | 0.233 |
miR-222 (high vs. low) | 1.03 (0.51-2.08) | 0.94 |
miR-21 (high vs. low) | 5.84 (2.79-12.28) | <0.001 |
miR-221 (high vs. low) | 1.51 (0.89-2.57) | 0.131 |
miR-181b (high vs. low) | 1.32 (0.75-2.33) | 0.340 |
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Pamedytyte, D.; Simanaviciene, V.; Dauksiene, D.; Leipute, E.; Zvirbliene, A.; Sarauskas, V.; Dauksa, A.; Verkauskiene, R.; Zilaitiene, B. Association of microRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer. Biomolecules 2020, 10, 625. https://doi.org/10.3390/biom10040625
Pamedytyte D, Simanaviciene V, Dauksiene D, Leipute E, Zvirbliene A, Sarauskas V, Dauksa A, Verkauskiene R, Zilaitiene B. Association of microRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer. Biomolecules. 2020; 10(4):625. https://doi.org/10.3390/biom10040625
Chicago/Turabian StylePamedytyte, Daina, Vaida Simanaviciene, Dalia Dauksiene, Enrika Leipute, Aurelija Zvirbliene, Valdas Sarauskas, Albertas Dauksa, Rasa Verkauskiene, and Birute Zilaitiene. 2020. "Association of microRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer" Biomolecules 10, no. 4: 625. https://doi.org/10.3390/biom10040625