Identification of a Four-Gene Signature for Determining the Prognosis of Papillary Thyroid Carcinoma by Integrated Bioinformatics Analysis

PURPOSE: Although well-differentiated papillary thyroid carcinoma (PTC) has an indolent nature and usually an excellent prognosis, some patients experience disease recurrence or death. The aim of this study was to identify prognostic markers to stratify PTC patients. PATIENTS AND METHODS: Eight gene-expression profiles (GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE53157, GSE60542, and GSE104005) were obtained from the Gene Expression Omnibus and used to analyze differentially expressed genes (DEGs) between PTC tissues and non-tumor tissues. Univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed to identify prognostic genes and establish a risk-score model based on the integrated DEGs. Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves were used to validate the prognostic performance of the risk score. A nomogram was constructed based on The Cancer Genome Atlas dataset and Multivariable Cox regression analysis. RESULTS: A total of 165 upregulated and 207 downregulated DEGs were screened. A four-gene signature including PAPSS2, PCOLCE2, PTX3, and TGFBR3 was identified. The risk-score model showed a strong diagnosis performance for identifying patients with a poor prognosis. KM analysis showed that patients with low risk scores had a significantly more favorable overall survival (OS) than those with high risk scores (p = 0.0002). ROC curves based on the four-gene signature showed better performances in predicting 1-, 3-, and 5-year survival than did the American Joint Committee on Cancer staging system (area under the curve: 0.86 vs 0.84, 0.80 vs 0.63, and 0.79 vs 0.73, respectively). Furthermore, when combined with age and tumor status from the nomogram, the four-gene signature achieved a good performance in guiding postoperative follow-up surveillance of patients with PTC. CONCLUSION: The four-gene signature was found to be a novel and reliable biomarker with great potential for clinical application in risk stratification and OS prediction in patients with PTC.