Table 2.
MicroRNAs as potential NEN biomarkers.
| miRNA | Characteristic miRNA as Candidates for NEN Markers |
Methods | Citation |
|---|---|---|---|
| NENs of different anatomical sites | |||
| miRNA-375, miRNA-7 | Increased expression levels in tumor tissue compared to control | MiRNA sequencing and data mining | [22] |
| Intestines | |||
| miRNA-375 | Increased expression in tumor biopsies compared to normal mucosa (p = 1.0 × 10−19). Can be considered as a prognostic marker. Highly expressed patients with liver metastases had significantly better survival (p = 0.016) | qRT- PCR | [24] |
| miRNA-1, miRNA-143 | Decreased expression associated with tumor progression (p < 0.05, p < 0.001) |
qRT-PCR | [6] |
| miRNA-31, miRNA-129-5p, miRNA-133a, miRNA-215 |
Decreased expression is associated with tumor progression (p < 0.05) |
qRT-PCR | [34] |
| miRNA-96, miRNA-182, miRNA-183, miRNA-196a miRNA-200a |
Increased expression associated with tumor progression (p < 0.05) |
qRT-PCR | [34] |
| miRNA-21-5p miRNA-22-3p |
Increased expression is associated with metastases (p < 0.0001) and decreased survival (OR = 0.47, 95% CI 0.27–0.82) | miRNA sequencing | [30] |
| miRNA-150-5p | Decreased expression is associated with the appearance of metastases (p = 0.027) | miRNA sequencing | [30] |
| miRNA-7-5p | Increased expression in tumor biopsies compared to normal mucosa (p = 4.2 × 10−19) |
Chip hybridization | [24] |
| miRNA-615, miRNA-92b | Increased midgut expression compared to non-midgut samples (p < 0.01) |
miRNA sequencing and qRT-PCR | [25] |
| miRNA125b, miRNA-192, miRNA-149 | Expression is significantly lower in iliac than in appendicular NENs (p < 0.01) |
miRNA sequencing and qRT-PCR | [25] |
| miRNA-186 | Expression decreased in tumor (p < 0.05) |
RT-PCR | [26] |
| Gastrointestinal tract | |||
| miRNA-96 | Increased expression in liver metastases compared with primary NENs (p < 0.05) | qRT-PCR | [31] |
| miRNA-133a | Decreased expression in liver metastases compared with primary NENs (p < 0.05) | qRT-PCR | [31] |
| miRNA-375 | Increased expression in all samples | miRNA sequencing and qRT-PCR | [25] |
| miRNA-202-3p | Expression increased in tumor tissue compared to normal tissue (p = 0.014) |
RT-PCR | [18] |
| miRNA-429 | Expression is significantly higher in rectal NENs compared to pancreatic ones (p < 0.01) | miRNA sequencing and qRT-PCR | [25] |
| miRNA-96-5p | Increased expression from G1 to G3 (p < 0.05) | RT-PCR | [19] |
| Pancreas | |||
| miRNA449a | Important role in proliferation and may be a potential predictor of poor survival | Microarrays | [66] |
| miRNA-196a | Increased expression is associated with decreased overall survival (p = 0.046). High expression indicates poor prognosis after pancreatic NEN resection. Recurrence HR = 16.26 |
Nanostring nCounter Analysis and qRT-PCR | [28] |
| miRNA-137 | Reduces survival, leading to increased tumor growth | RNA sequencing | [37] |
| miRNA-224 | Increased expression increases apoptosis and decreases proliferation (p < 0.05) | RT-PCR | [38] |
| miRNA-23b | Increased expression during metastasing | RNA sequencing | [37] |
| miRNA-3653 | Increased expression associated with risk of metastasis (p < 0.05) | MiRNA microarray | [36] |
| miRNA-193b | An increase in expression with NENs was found not only in tissue but also in serum (p < 0.05) | RT-PCR | [33] |
| Lungs | |||
| miRNA-92a-2 | Increased expression is associated with chemoresistance (p = 0.010) and decreased survival (p = 0.007) | RT-PCR | [42] |
| miRNA-147 | Increased expression associated with chemoresistance (p = 0.018) | RT-PCR | [42] |
| miRNA-574-5p | Increased expression associated with chemoresistance (p = 0.039) | RT-PCR | [42] |
| let-7d, miRNA-19, miRNA576-5p, miRNA-340 * miRNA-1286 |
High expression levels are associated with survival (p < 0.05) | Q-PCR | [46] |
| miRNA-21 | An increase in the level of expression correlated with an increase in the grade of malignancy (p = 0.00033). | Q-PCR | [41] |
| miRNA-34a | High expression levels associated with atypical carcinoids (p = 0.010) | Q-PCR | [41] |
| miRNA-18a miRNA -155 | Increased expression allows low-grade carcinoids to be distinguished from high-grade carcinoids with a high degree of accuracy (>90%). Diagnostic marker | Sequencing | [21] |
| miRNA-17, miRNA-103, miRNA-127 | Candidate markers for distinguishing between typical and atypical carcinoids. Accuracy 93% | Sequencing | [21] |
| miRNA-301a, miRNA-106b miRNA-25 | Candidate markers for distinguishing small cell lung carcinoma and large cell neuroendocrine carcinoma. Accuracy 100% | Sequencing | [21] |
| miRNA-375-3p | Distinguishes low-grade neuroendocrine lung tumors from non-neuroendocrine lung tumors with 92.6% of sensitivity and 90.4% of specificity | qRT-PCR | [39] |
| miRNA-21, miRNA-155 | Increased expression in high-grade tumors compared to carcinoid tumors (each p < 0.001). The expression level of miR-21 in carcinoid tumors with metastases to lymph nodes is higher than in carcinoid tumors without metastases to lymph nodes (p = 0.010) | qRT-PCR | [40] |
*—The expression level of miRNA-340 depends on the properties of the tumor.