Identification and validation of potential novel biomarkers to predict distant metastasis in differentiated thyroid cancer

Abstract

Background: Distant metastasis (DM) is not common in differentiated thyroid cancer (DTC). However, it is associated with a significantly poor prognosis. Early detection of high-risk DTC patients is difficult, and the molecular mechanism is still unclear. Therefore, the present study aims to establish a novel predictive model based on clinicopathological parameters and DM-related gene signatures to provide guidelines for clinicians in decision making. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to discover coexpressed gene modules and hub genes associated with DM. Univariate and multivariate analyses were carried out to identify independent clinicopathological risk factors based on The Cancer Genome Atlas (TCGA) database. An integrated nomogram prediction model was established. Finally, real hub genes were validated using the GSE60542 database and various thyroid cell lines. Results: The midnightblue module was most significantly positively correlated with DM (R=0.56, P=9e-06) by as per WGCNA. DLX5 (AUC: 0.769), COX6B2 (AUC: 0.764), and LYPD1 (AUC: 0.760) were determined to be the real hub genes that play a crucial role in predicting DM. Meanwhile, univariate and multivariate analyses demonstrated that T-stage (OR, 15.03; 95% CI, 1.75-319.40; and P=0.024), histologic subtype (OR, 0.17; 95% CI, 0.03-0.92; and P=0.042) were the independent predictors of DM. Subsequently, a nomogram model was constructed based on gene signatures and independent clinical risk factors exhibited good performance. Additionally, the mRNA expressions of real hub genes in the GSE60542 dataset were consistent with TCGA.Conclusions: The present study has provided a reliable model to predict DM in patients with DTC. This model is likely to serve as an individual risk assessment tool in therapeutic decision-making.

Nomogram individually predicts the risk for distant metastasis and prognosis value in female differentiated thyroid cancer patients: A SEER-based study

“…Thyroid cancer patients who develop DM are reported to have a poor prognosis and low overall survival ( 20 ). During the past decades, many studies have focused on identifying the heterogeneous and homogeneous prognosis-related factors of DM, including male gender, tumor size, histology subtype, extrathyroidal extension, age at diagnosis, and lymph node metastasis status ( 6 , 8 , 21 – 24 ). However, the potential impact of gender disparity on thyroid cancer prognosis was ignored.…”

Can Cervical Lymph Node Metastasis Increase the Risk of Distant Metastasis in Papillary Thyroid Carcinoma?

“…In contrast, N1a disease could not increase the risk of DM in patients with PTC. Surprisingly, further investigations on this relationship conducted by Wang (8) proved that LNM had no significant influence on DM. The conflicting results were partly attributable to neglecting the influence of potential confounding factors (advanced age, male gender, tumor size, and BRAF-V600E) on DM and simply exploring the risk factors that affect the overall DM without considering the heterogeneity of different metastatic sites.…”

“…Distant metastasis (DM), including lung metastasis (LM), bone metastasis (BM), brain metastasis, and liver metastasis, contributes to the leading cause of thyroid cancer-related death (8), and the rates of 5-and 10-year cancer-specific survival (CSS) for PTC patients with DM were reported to be 35 and 25%, respectively (9,10). Previous studies pointed out that LNM was considered as the strongest predictor of DM (11)(12)(13), especially in younger patients (<55 years) (14).…”

Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer

“…The incidence of thyroid cancer (TC) has been increasing in recent years and papillary TC (PTC) is the most frequent histological type that derives from follicular cells, accounting for up to 85% of cases [ 1 ]. Although the vast majority of patients with PTC have a favorable prognosis via reasonable treatments, including thyroidectomy, thyroid-stimulating hormone (TSH) suppressive therapy, and radioactive iodine (RAI) therapy, approximately 10–20% of PTCs suffer from disease recurrence and progress to distant metastasis during follow-up [ 2 ]. Among these patients, dedifferentiation is the main reason that leads to PTC transform into poorly differentiated or anaplastic TC (ATC) with poor clinical outcome.…”