RESUMEN
Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.
RESUMEN
BACKGROUND: To treat secondary hyperparathyroidism with subtotal parathyroidectomy or total parathyroidectomy with autotransplantation might cause the disease to recur because of growth of the parathyroid remnant or the autografts. The aim of the present study was to determinate an alternative surgical treatment for secondary hyperparathyroidism. METHODS: Of 94 uremic patients, 44 (median age: 50.5 years; 33 women/11 men) were assigned to group A, patients who were not expected to receive kidney transplantation for various reasons and had total parathyroidectomy without autotransplantation; 50 (median age 46 years; 33 women/17 men) were assigned to group B, patients who had either total parathyroidectomy with autotransplantation or subtotal total parathyroidectomy with preservation of parathyroid tissue in situ. Parameters measured included demographics, perioperative and follow-up biochemistry tests, operative time, postoperative complications, length of hospital stay, patients' compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D supplementation regimen, symptom relief, and presence of recurrence. RESULTS: Mean operative times were 103 and 122 min (P = 0.007); postoperative complication rates were 18.2% and 12.0% (P = 0.563); mean hospital stays were 6 and 9 days (P = 0.259); adequate patient compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D regimens were 84.1% and 78.0%, respectively (P = 0.6); symptom relief rates were 88.6% and 80.0% (P = 0.277). Recurrence rates over 60 months in group A and group B were 4.5% and 18.0%, resectively (P = 0.028 by Kaplan-Meier analysis). CONCLUSIONS: Because of the lower recurrent rate and shorter operative time, total parathyroidectomy without autotransplantation may be an option for treating patients with symptomatic secondary hyperparathyroidism who are not expected to receive kidney transplantation.