Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer
Abstract
:1. Introduction
2. Results
2.1. TCGA Methylation Data Analysis
2.2. TCGA Gene and miRNA Expression Analysis
2.3. Gene Expression Analysis
2.4. miR-205-5p Expression
2.5. ROC Curves for the Combination of Candidate Targets
2.6. Correlation of the Expression Data
3. Discussion
4. Materials and Methods
4.1. Selection of Study Group
4.2. TCGA Methylation Data Analysis
4.3. TCGA Gene and miRNA Expression Analysis
4.4. RNA/DNA Extraction
4.5. Gene Expression Analysis
4.6. miR-205-5p Expression Analysis
4.7. ROC Curve Analysis Using CombiROC Sofrware
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Normal vs. CIN | Normal vs. Cancer | CIN vs. Cancer | ||||||
---|---|---|---|---|---|---|---|---|
Combination | Candidates | AUC | Combination | Candidates | AUC | Combination | Candidates | AUC |
Combo I | MEG3 + MLH1 + miR-205-5p | 0.876 | Combo I | MEG3 + miR-205-5p | 0.954 | Combo I | MEG3 + TIMP3 | 0.782 |
Combo II | MEG3 + TIMP3 + miR-205-5p | 0.881 | Combo II | TIMP3 + miR-205-5p | 0.944 | Combo II | MEG3 + miR-205-5p | 0.82 |
Combo III | MLH1 + TIMP3 + miR-205-5p | 0.907 | Combo III | MEG3 + TIMP3 + miR-205-5p | 0.951 | Combo III | MEG3 + TIMP3 + miR-205-5p | 0.82 |
Combo IV | MEG3 + MLH1 + TIMP3 + miR-205-5p | 0.9 |
p Value | MEG3 | TIMP3 | DAPK1 | MLH1 | SOX1 | MALAT1 | miR-205-5p |
---|---|---|---|---|---|---|---|
MEG3 | 0.9832 | 0.0005 | 1.74 × 10−14 | 0.8237 | 9.11 × 10−5 | 2.89 × 10−5 | |
TIMP3 | 0.9832 | 0.0012 | 0.8836 | 0.7740 | 0.0981 | 0.9408 | |
DAPK1 | 0.0005 | 0.0012 | 5.49 × 10−10 | 0.4147 | 5.20 × 10−14 | 0.0033 | |
MLH1 | 1.74 × 10−14 | 0.8836 | 5.49 × 10−10 | 0.6617 | 4.36 × 10−19 | 0.0199 | |
SOX1 | 0.8237 | 0.7740 | 0.4147 | 0.6617 | 0.6888 | 0.7545 | |
MALAT1 | 9.11 × 10−5 | 0.0981 | 5.20 × 10−14 | 4.36 × 10−19 | 0.6888 | 0.3439 | |
miR-205-5p | 2.89 × 10−5 | 0.9408 | 0.0033 | 0.0199 | 0.7545 | 0.3439 |
Demographics | CESC (n = 304) | Cervical Cancer (9) | CIN (30) | Normal (38) | |
---|---|---|---|---|---|
Age | Median, Range ♀ | 46, 20–88 | 43, 29–64 | 39, 22–63 | 44, 28–65 |
HPV Status | Positive | 281 | 9 | 29 | 30 |
Negative | 22 | 0 | 1 | 8 | |
Indeterminate | 1 | 0 | |||
Pathologic TNM | T1 | 140 | 5 | ||
T2 | 71 | ||||
T3 | 20 | ||||
T4 | 10 | ||||
Tis | 1 | ||||
Tx | 17 | ||||
T unknown | 45 | 4 | |||
N0 | 133 | 5 | |||
N1 | 60 | ||||
Nx | 66 | ||||
N unknown | 45 | 4 | |||
M0 | 116 | 5 | |||
M1 | 10 | ||||
Mx | 128 | ||||
M unknown | 50 | 4 | |||
Clinical stage | I | 162 | 1 | ||
II | 69 | 2 | |||
III | 45 | 1 | |||
IV | 21 | ||||
Unknown | 7 | 5 | |||
Birth control pill use | Current user | 15 | 1 | 4 | 4 |
Former user | 53 | 3 | 12 | 15 | |
Never used | 89 | 5 | 14 | 19 | |
NA | 147 | ||||
Histological type | Adenosquamous | 5 | |||
Cervical squamous cell carcinoma | 252 | 9 | |||
Endocervical adenocarcinoma of the usual type | 6 | ||||
Endocervical type of adenocarcinoma | 21 | ||||
Endometroid adenocarcinoma of endocervix | 3 | ||||
Mucinous adenocarcinoma of endocervical type | 17 | ||||
Tobacco smoking history | Lifelong non-smoker | 144 | 5 | 17 | 24 |
Current smoker | 64 | 4 | 13 | 14 | |
Reformed smoker > 15 years | 9 | ||||
Reformed smoker ≤ 15 years | 40 | ||||
Reformed smoker duration unknown | 4 | ||||
NA | 43 |
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Dudea-Simon, M.; Mihu, D.; Pop, L.A.; Ciortea, R.; Malutan, A.M.; Diculescu, D.; Ciocan, C.A.; Cojocneanu, R.M.; Simon, V.; Bucuri, C.; et al. Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer. Int. J. Mol. Sci. 2022, 23, 6054. https://doi.org/10.3390/ijms23116054
Dudea-Simon M, Mihu D, Pop LA, Ciortea R, Malutan AM, Diculescu D, Ciocan CA, Cojocneanu RM, Simon V, Bucuri C, et al. Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer. International Journal of Molecular Sciences. 2022; 23(11):6054. https://doi.org/10.3390/ijms23116054
Chicago/Turabian StyleDudea-Simon, Marina, Dan Mihu, Laura Ancuta Pop, Razvan Ciortea, Andrei Mihai Malutan, Doru Diculescu, Cristina Alexandra Ciocan, Roxana Maria Cojocneanu, Vasile Simon, Carmen Bucuri, and et al. 2022. "Alteration of Gene and miRNA Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer" International Journal of Molecular Sciences 23, no. 11: 6054. https://doi.org/10.3390/ijms23116054