Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study
Abstract
:1. Introduction
2. Methods
2.1. Patients
2.2. Log2FC and Power Transformation for miRNA and mRNA
2.3. Selection of RNAs to Predict Clinical End Points
2.4. Network Analysis
2.5. Ingenuity Pathway Analysis
3. Results
3.1. Early Progression and Tumor Stage
3.2. Selection of miRNAs That Predicted Early Progression and Tumor Stage Better
3.3. Selection of RNAs According to Disease and Biological Functions Using IPA
3.4. Association between Unresolved Inflammation and Early Progression in miRNA-mRNA Simplified Network Analysis
3.5. Association between Systemic Tumor Microenvironment and Metastasis in miRNA-mRNA Simplified Network Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All | Early Progression | p | ||
---|---|---|---|---|
(N = 28) | No (N = 21) | Yes (N = 7) | ||
Age (years) (IQR) | 50.0 (42.5;56.0) | 50.0 (47.0;56.0) | 46.0 (35.0;51.5) | 0.184 |
FIGO staging 2018, n (%) | 0.298 | |||
- IB | 4 (14.3%) | 3 (14.3%) | 1 (14.3%) | |
- IIB-IIIC1 | 14 (50.0%) | 12 (57.1%) | 2 (28.6%) | |
- IIIC2-IVA | 7 (25.0%) | 5 (23.8%) | 2 (28.6%) | |
- IVB | 3 (10.7%) | 1 (4.8%) | 2 (28.6%) | |
Pathology, n (%) | 0.017 | |||
- Adenocarcinoma | 4 (14.3%) | 1 (4.8%) | 3 (42.9%) | |
- Adenosquamous cell carcinoma | 1 (3.6%) | 0 (0.0%) | 1 (14.3%) | |
- Unclassified carcinoma | 1 (3.6%) | 1 (4.8%) | 0 (0.0%) | |
- Squamous cell carcinoma | 22 (78.6%) | 19 (90.5%) | 3 (42.9%) | |
RT field, n (%) | 0.815 | |||
Pelvis | 19 (67.9%) | 15 (71.4%) | 4 (57.1%) | |
Pelvis with para-aortic region | 9 (32.1%) | 6 (28.6%) | 3 (42.9%) | |
Total dose (EQD2) (IQR) | 76.2 (72.2;84.2) | 75.5 (72.2;84.2) | 84.2 (74.2;84.2) | 0.357 |
Intracavitary brachytherapy, n (%) | 0.483 | |||
- No treatment | 2 (7.1%) | 1 (4.8%) Refusal | 1 (14.3%) EBRT | |
- 24 Gy in four fractions | 10 (35.7%) | 9 (42.9%) | 1 (14.3%) | |
- 24 Gy in six fractions | 5 (17.9%) | 4 (19.0%) | 1 (14.3%) | |
- 25 Gy in five fractions | 1 (3.6%) | 1 (4.8%) | 0 (0.0%) | |
- 30 Gy in six fractions | 10 (35.7%) | 6 (28.6%) | 4 (57.1%) | |
Dexamethasone during RT, n (%) | 1.000 | |||
No | 21 (75.0%) | 16 (76.2%) | 5 (71.4%) | |
Yes | 7 (25.0%) | 5 (23.8%) | 2 (28.6%) | |
Dexamethasone after RT, n (%) | 0.061 | |||
No | 24 (85.7%) | 20 (95.2%) | 4 (57.1%) | |
Yes | 4 (14.3%) | 1 (4.8%) | 3 (42.9%) | |
Death, n (%) | 0.014 | |||
No | 25 (89.3%) | 21 (100.0%) | 4 (57.1%) | |
Yes | 3 (10.7%) | 0 (0.0%) | 3 (42.9%) |
Regulatory miRNAs | mRNAs | Related Function | References |
---|---|---|---|
Pro-inflammation | |||
miR-1228-5p↓, miR-33a-5p↓, miR-146a-3p↑ | PDE3A↓ | Cardiac contractility↑ Vascular contractility↑ | [15] |
miR-1228-5p↓, miR-146a-3p↑ | ADAMTS-18↓ | Platelet activation↑ | [16] |
miR-3200-3p↓ | TG↑ | Inflammatory cytokine↑ Cancer proliferation↑ | [17,18] |
miR-33a-5p↓ | HIST2H2AA3/4↓ | DNA damage↑ | [19] |
miR-3200-3p↓ | PLCE1↑ | Inflammatory cytokine↑ Cancer proliferation↑ | [20] |
miR-3200-3p↓ | GCNT3↑ | Inflammatory cytokine↑ | [21,22] |
miR-146a-3p↑ | PHYH↑ | Peroxisome ↑ | [23] |
miR-6815-5p↓ | TNIP1↓ | Anti-inflammation↓ | [24] |
miR-6815-5p↓ | RSPH3↓ | Inflammatory cytokine↑ | [25,26] |
Anti-inflammation | |||
miR-1228-5p↓, miR-33a-5p↓, miR-146a-3p↑ | PDE3A↓ | Platelet aggregation↓ | [15] |
miR-146a-3p↑ | PLAUR↓ | Plasminogen activation↓ | [27] |
miR-33a-5p↓ | PTGS1↓ | Prostaglandins↓ -> anti-inflammation↑ | [28] |
miR-1228-5p↓ | DHCR24↓ | Inflammatory gene expression↓ | [29] |
miR-146a-3p↑ | E2F2↓ | Inflammatory signal↓ | [30] |
miR-3200-3p↓ | CCKBR↑ | Vagus nerve stimulation -> anti-inflammation↑ | [31] |
Cell mediated immunity↓ | |||
miR-1228-5p↓, miR-146a-3p↑ | SLAMF1↑ | Activation of macrophages↓ | [32] |
miR-1228-5p↓, miR-3200-3p↓ | FCGR1A↓ | Antigen presentation↓ | [33] |
miR-1228-5p↓ | C1QB↓ | Antigen presentation↓ | [34] |
Blood glucose↑ | |||
miR-3200-3p↓ | NUBPL↑ | Mitochondrial complex 1↑ -> Blood glucose↑ | [35,36] |
miR-1228-5p↓, miR-146a-3p↑ | PCK1↑ | Blood glucose↑ | [37] |
miR-1228-5p↓, miR-146a-3p↑ | STX16↓ | Intracellular glucose transport↓ | [38] |
miR-3200-3p↓ | ADCY8↑ | Obese and type 2 diabetes | [39] |
miR-3200-3p↓ | IP6K3↑ | Blood glucose↑ | [40] |
miR-3200-3p↓ | NEGR1↑ | Obese and insulin resistance↑ | [41] |
Cancer progression | |||
miR-1228-5p↓, miR-146a-3p↑ | NAV3↓ | Cancer metastasis↑ | [42] |
miR-1228-5p↓ | LARGE1↓ | Cancer metastasis↑ | [43] |
miR-33a-5p↓ | PSD3↓ | Cancer proliferation↑ | [44] |
miR-146a-3p↑ | CCNO↑ | Cancer proliferation↑ | [45] |
miR-6815-5p↓ | miR-590-3p↑ | Cancer progression↑ | [46] |
Unclassified | |||
miR-33a-5p↓ | ACVR1↓ | Oncogene vs. tumor suppressor gene | [47] |
miR-3200-3p↓ | TYMP↓ | Cancer proliferation↓ vs. chemo response↓ | [48] |
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Cho, O.; Kim, D.-W.; Cheong, J.-Y. Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study. J. Clin. Med. 2021, 10, 2110. https://doi.org/10.3390/jcm10102110
Cho O, Kim D-W, Cheong J-Y. Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study. Journal of Clinical Medicine. 2021; 10(10):2110. https://doi.org/10.3390/jcm10102110
Chicago/Turabian StyleCho, Oyeon, Do-Wan Kim, and Jae-Youn Cheong. 2021. "Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study" Journal of Clinical Medicine 10, no. 10: 2110. https://doi.org/10.3390/jcm10102110