Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors
Abstract
:1. Introduction
2. Results
2.1. Clinical Features of PHPT Patients Harbouring PAds
2.2. Gene Expression by Real-Time PCR
2.3. Unsupervised Clustering Analysis
2.4. Selected mRNA, miRNA, and lncRNA Expression Profiles in the Different PAd Clusters
2.5. Clinical Features Associated with the Different Gene Profiles
2.6. Prediction of Intracellular Pathway Deregulated in PAds
3. Discussion
4. Materials and Methods
4.1. Parathyroid Tumor Samples
4.2. RNA Extraction
4.3. Real-Time PCR
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Cluster 1 | Cluster 2A | Cluster 2B | p |
---|---|---|---|---|
Oncosuppressors | ||||
MEN1 | 1.921 ± 0.718 | 1.706 ± 0.555 | 0.770 ± 0.290 *,** | <0.0001 |
CDC73 | 2.034 ± 1.046 | 1.252 ± 0.441 * | 0.806 ± 0.269 * | 0.0001 |
RASSF1A | 1.417 (0.788, 2.022) | 1.596 (1.155, 2.578) | 0.836 (0.542, 1.048) ** | 0.0439 |
YAP1 | 2.033 ± 1.210 | 1.403 ± 0.450 | 0.788 ± 0.324 * | 0.0004 |
CTNNB1 | 2.198 ± 1.290 | 1.511 ± 1.028 | 0.877 ± 0.421 * | 0.0021 |
Transcription factors | ||||
GCM2 | 1.693 ± 0.955 | 2.315 ± 0.713 | 0.713 ± 0.357 * | <0.0001 |
GATA3 | 1.629 (1.260, 2.498) | 1.202 (0.819, 1.462) | 0.857 (0.580, 1.040) * | 0.0041 |
TBX1 | 1.157 (0.704, 2.010) | 1.711 (1.027, 2.211) | 0.806 (0.540, 1.091) | 0.1292 |
PAX1 | 2.058 (0.854, 2.884) | 0.803 (0.533, 2.012) | 1.089 (0.515, 1.308) | 0.0742 |
Parathyroid-specific genes | ||||
PTH | 2.577 (1.393, 7.689) | 1.218 (0.488, 3.108) | 0.811 (0.509, 1.123) * | 0.0052 |
CASR | 2.380 ± 1.252 | 1.833 ± 1.252 | 0.756 ± 0.313 *,** | 0.0001 |
VDR | 2.972 (0.868, 3.417) | 1.298 (0.915, 2.201) | 0.713 (0.498, 1.206) * | 0.0252 |
GPRC6A | 0.999 (0.542, 2.569) | 2.092 (0.931, 4.779) | 0.983 (0.364, 2.262) | 0.4753 |
Cell cycle genes | ||||
CCND1 | 2.340 (0.685, 5.710) | 1.484 (0.873, 2.008) | 0.676 (0.502, 0.954) *,** | 0.0058 |
CDKN1B/p27 | 3.723 ± 2.229 | 0.809 ± 0.982 * | 1.039 ± 0.634* | <0.0001 |
CDKN1A/p21 | 2.342 (1.186, 4.633) | 1.227 (0.193, 2.820) | 1.025 (0.292, 1.681) | 0.0679 |
TP73 | 1.232 (0.579, 14.48) | 0.213 (0.213, 6.900) | 0.511 (0.213, 5.485) | 0.0930 |
MicroRNAs | ||||
miR-372-5p | 0.268 (0.194, 2.463) | 0.532 (0.304, 24.51) | 0.353 (0.231, 0.927) | 0.5641 |
miR-517c | 0.217 (0.052, 0.752) | 0.098 (0.061, 7674) | 0.424 (0.135, 1.628) | 0.2115 |
miR-126-3p | 0.744 ± 0.504 | 0.951 ± 0.498 | 1.270 ± 0.502 | 0.0507 |
miR-93-5p | 0.681 ± 0.423 | 1.173 ± 0.412 | 1.068 ± 0.396 | 0.0560 |
Long non-coding RNAs | ||||
NEAT1 | 2.386 (1.636, 6.208) | 2.285 (1.629, 3.635) | 0.641 (0.402, 0.966) *,** | <0.0001 |
HAR1B | 2.059 (0.519, 15.45) | 0.130 (0.075, 0.698) * | 2.507 (0.467, 3.592) ** | 0.0371 |
HOXA-AS2 | 0.348 (0.092, 1.871) | 9.099 (3.443, 16.30) * | 0.866 (0.079, 1.496) ** | 0.0125 |
HOXA-AS3 | 0.458 (0.458, 1.049) | 4.784 (2.910, 11.92) * | 0.458 (0.458, 1.302) ** | 0.0028 |
VLDLR-AS1 | 2.279 (1.278, 3.423) | 1.976 (0.812, 2.556) | 0.760 (0.303, 1.521) * | 0.0139 |
SNHG6 | 1.681 (0.875, 2.607) | 0.795 (0.509, 1.917) | 0.971 (0.513, 1.383) | 0.1202 |
Features | n.v. | Cluster 1 | Cluster 2A | Cluster 2B | p |
---|---|---|---|---|---|
General and tumor features | |||||
Female/male (%) | - | 8/0 (100.0) * | 2/3 (40.0) | 15/4 (78.9) | 0.0388 |
Age (years) | - | 55.3 ± 7.8 | 59.8 ± 12.3 | 58.3 ± 11.2 | 0.2583 |
BMI (kg/m2) | - | 23.7 ± 2.6 | 24.7 ± 1.8 | 25.6 ± 6.0 | 0.2863 |
Tumor size (cm) | - | 1.88 ± 1.03 | 1.98 ± 0.38 | 1.27 ± 0.51 | 0.0376 |
Biochemical and hormonal parameters | |||||
Ca2+ (mmol/L) | 1.15–1.29 | 1.46 (1.35, 1.63) | 1.62 (1.53, 2.33) | 1.41 (1.38, 1.49) * | 0.0398 |
S Total Ca (mg/dL) | 8.4–10.4 | 11.9 ± 1.2 | 14.7 ± 4.5 | 11.3 ± 0.7 * | 0.0097 |
S Phosphate (mg/dL) | 3.5–5.0 | 2.7 ± 0.7 | 2.5 ± 0.6 | 2.1 ± 0.7 | 0.2479 |
PTH (pg/mL) | 10.0–65.0 | 170.5 (110.5, 372.5) | 301.0 (195.0, 1031.0) | 135.0 (88.1, 173.8) * | 0.0427 |
eGFR (mL/min) | >90.0 | 85.8 ± 18.6 | 85.7 ± 16.5 | 83.2 ± 13.0 | 0.9278 |
UCa (mg/24 h) | <300.0 | 430.4 ± 183.6 | 451.4 ± 65.4 | 360.6 ± 128.9 | 0.3214 |
PHPT-related complications | |||||
Kidney stones (y/n, %) | - | 4/4 (50.0) | 3/2 (60.0) | 8/11 (42.1) | 0.7593 |
Osteoporosis (y/n, %) | - | 6/2 (75.0) | 4/1 (80.0) | 10/9 (52.6) | 0.3723 |
Hypertension (y/n, %) | - | 4/4 (50.0) | 1/4 (20.0) | 5/14 (26.3) | 0.4027 |
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Verdelli, C.; Carrara, S.; Maggiore, R.; Dalino Ciaramella, P.; Corbetta, S. Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors. Int. J. Mol. Sci. 2024, 25, 10782. https://doi.org/10.3390/ijms251910782
Verdelli C, Carrara S, Maggiore R, Dalino Ciaramella P, Corbetta S. Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors. International Journal of Molecular Sciences. 2024; 25(19):10782. https://doi.org/10.3390/ijms251910782
Chicago/Turabian StyleVerdelli, Chiara, Silvia Carrara, Riccardo Maggiore, Paolo Dalino Ciaramella, and Sabrina Corbetta. 2024. "Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors" International Journal of Molecular Sciences 25, no. 19: 10782. https://doi.org/10.3390/ijms251910782