From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Circulating Tumor Cells
3. Cell-Free DNA
4. MicroRNAs (miRNAs)
4.1. miRNA Detection
- (1)
- The use of profiling methods, such as microarray, quantitative real-time polymerase chain reaction (qRT-PCR)-based array, quantitative nCounter, or next-generation sequencing (NGS), to quantify hundreds of miRNAs in samples obtained from patients with a pathology of interest in comparison to control subjects. This approach is usually followed by the validation of identified miRNAs using qRT-PCR or other techniques.
- (2)
- The selection of a subset of specific miRNAs related to specific tissues, cells, gene expression pathways, and diseases. In this case, the number of miRNAs to study is limited, and other experimental approaches can be used. These include individual qRT-PCR, which allows increasing sensitivity and reproducibility of the analysis, and droplet digital PCR technology, which provides miRNA absolute quantification without the requirement of standard curves, efficiency correction methods, or technical replicates [41].
4.2. Circulating miRNAs in MTC
5. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Ref. |
Number of Analyzed MTC Patients | Technique |
Peripheral Blood mL | Results |
---|---|---|---|---|
[23] | 12 | CanPatrol capture | 5 |
7/12 (58.3%) CTC-positive 5/12 (41.6%) CTC-negative |
[24] | 30 | CanPatrol capture | 5 | >6 CTCs worst prognosis (up to 60 months) |
[25] | 18 | Veridex Cell Search | 7.5 | >5 CTCs worst prognosis |
[26] | 9 | ScreenCell device | 7.5 | 8/9 (89%) CTC-positive |
[27] | 14 |
BD Vacutainer Cell Preparation Tubes | 8 | ±5 cells in MTC patients |
miRNA | Source | Sample Size | Approach | Results | Ref. |
---|---|---|---|---|---|
miR-375 | Plasma |
Discovery cohort:
19 MTC patients 19 healthy control subjects Validation cohort: 17 MTC patients 17 healthy control subjects Vandetanib treatment: 20 MTC patients |
Microarray profiling qRT-PCR validation |
miR-375 was up-regulated in MTC patients vs. healthy controls ( AUC 0.85 for the discovery cohort and 0.75 for the validation cohort); High levels were associated with a significantly reduced overall survival (HR = 10.61, p < 0.0001); miR-375 plasma levels were not predictive of vandetanib response. | [44] |
miR-222-3p miR-17-5p | Serum |
15 MTC patients 91 patients with benign nodules 89 healthy controls |
TaqMan low-density array qRT-PCR validation |
miR-222-3p and miR-17-5p were significantly increased in the MTC group vs. benign nodule (AUC = 0.907) and control group (AUC = 1.000); They may serve as auxiliary tools for diagnosing MTC. | [45] |
miR-144 miR-34 | Plasma |
50 MTC patients (25 RET-positive and 25 RET-negative) 50 control subjects | qRT-PCR |
miR-144 and miR-34a were up-regulated in MTC patients vs. healthy controls, with higher levels in RET-positive patients; However, they showed no significant prognostic value as MTC biomarkers. | [46] |
miR-375 | Serum |
69 MTC patients 49 patients with non-C cell 14 patients with pheochromocytoma 19 healthy controls | qRT-PCR |
miR-375 levels were >100 times higher in MTC patients than in all other patients and controls; Negative correlation between miR-375 and CT miR-375 levels may be used as a marker in MTC diagnosis, with a high specificity (AUC = 0.978). | [47] |
miR-144-3p miR-7-5p miR-335-5p miR-375 | Serum |
2 MTC patients 34 healthy controls |
Small RNA-seq qRT-PCR |
miR144-3p, miR7-5p and miR335-5p were upregulated in MTC; miR-375 levels were significantly increased in all the different NEN subgroups. | [48] |
miR-26b-5p miR-451a | pEV |
Discovery cohort:
25 MTC patients 22 healthy controls Validation cohort: 12 MTC patients 13 control subjects |
MiRNA-TaqMan array Digital PCR |
miR-26b-5p and miR-451 were highly expressed in MTC patients; Their expression decreased during follow-up in disease-free patients; ROC curve analyses showed a high diagnostic and post-surgery role (AUC = 0.87 for miR-26b-5p and 0.83 for miR-451). | [49] |
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Ricci, C.; Salvemini, A.; Dalmiglio, C.; Castagna, M.G.; Cantara, S. From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer. Cancers 2023, 15, 4009. https://doi.org/10.3390/cancers15154009
Ricci C, Salvemini A, Dalmiglio C, Castagna MG, Cantara S. From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer. Cancers. 2023; 15(15):4009. https://doi.org/10.3390/cancers15154009
Chicago/Turabian StyleRicci, Claudia, Antonia Salvemini, Cristina Dalmiglio, Maria Grazia Castagna, and Silvia Cantara. 2023. "From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer" Cancers 15, no. 15: 4009. https://doi.org/10.3390/cancers15154009