Abstract

Background: Accurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circular RNAs (circRNAs) via the ceRNA mechanism could help establish a novel assessment tool.Methods: ceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. least absolute shrinkage and selection operator (LASSO)–Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.Results: Six hub DE-mRNAs, namely, CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC, and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the American Thyroid Association risk stratification system and distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size (MACIS) score American Joint Committee on Cancer staging system.Conclusions: Based on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

Highlights

  • Thyroid cancer, originating from thyroid follicular epithelial cells, is the most common malignancy of the endocrine system (La Vecchia et al, 2015)

  • DEcircRNAs, miRNAs, and mRNAs between papillary thyroid carcinoma (PTC) and normal thyroid tissues were identified after normalization of expression data

  • Six hub DEmRNAs, namely, CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the progression-free interval (PFI) of PTC, which were regulated by three DE-miRNAs, including hsa-miR-146b-3p, hsa-miR-139-5p, and hsa-miR139-3p

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Summary

Introduction

Thyroid cancer, originating from thyroid follicular epithelial cells, is the most common malignancy of the endocrine system (La Vecchia et al, 2015). Thyroid cancer is currently the eighth most common malignancy around the world (Antonelli and La Motta, 2017), and its incidence is rapidly increasing worldwide. Assessing Progression Risk of PTC carcinoma (PTC), follicular thyroid carcinoma, anaplastic thyroid carcinoma, and medullary thyroid carcinoma. Among all types of thyroid cancer, PTC has the highest incidence with a higher proportion of young patients. Most PTCs grow slowly, and 90% of patients have a relatively good prognosis after treatment, with a low post-operative recurrence rate

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