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

Abstract

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.

Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy

“…Principal component analysis (PCA) was conducted to evaluate the separation of low- and high-risk THCA ( 17 ). To further validate the advantage and stability of the novel signature, the C-index of our signature and other three models was compared ( 18 – 20 ).…”

The crossroad between autoimmune disorder, tissue remodeling and cancer of the thyroid: The long pentraxin 3 (PTX3)

“…Two different gene signatures including PTX3 were identified for the subtypes arising from the follicular cells: papillary, follicular and anaplastic. These new evidences suggest that the molecule could be an independent prognostic factor for most of the thyroid carcinomas ( 54 ), and a diagnostic tool to differentiate the anaplastic thyroid carcinoma from the other two subtypes ( 55 ).…”

“…A recent study identified a four genes signature including PTX3, 3′-phosphoadenosine 5′-phosphosulfate synthase 2 (PAPSS2), procollagen C-endopeptidase enhancer 2 (PCOLCE2) and transforming growth factor beta receptor 3 (TGFBR3) for papillary carcinoma as marker for risk stratification and survival prediction ( 54 ). PTX3 expression was significantly lower in patients surviving with tumors than in tumor free patients, revealing a potential correlation between PTX3 and tumor recurrence.…”

Reveal the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of papillary thyroid cancer

“…LINC01089 can block the malignant progression of TC by binding hsa-miR-27b-3p to increase the level of FBLN5 protein [ 31 ]. TGFBR3 expression is down-regulated in PTC tissues and is associated with OS of patients [ 32 ]. Herein, hsa_circ_0070100-hsa-miR-27a-3p/hsa-miR-27b-3p-TGFBR3 axis was identified.…”