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1.
Front Endocrinol (Lausanne) ; 13: 775278, 2022.
Article in English | MEDLINE | ID: mdl-35528004

ABSTRACT

Objective: This study aims to identify reliable prognostic biomarkers for differentiated thyroid cancer (DTC) based on glycolysis-related genes (GRGs), and to construct a glycolysis-related gene model for predicting the prognosis of DTC patients. Methods: We retrospectively analyzed the transcriptomic profiles and clinical parameters of 838 thyroid cancer patients from 6 public datasets. Single factor Cox proportional risk regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) were applied to screen genes related to prognosis based on 2528 GRGs. Then, an optimal prognostic model was developed as well as evaluated by Kaplan-Meier and ROC curves. In addition, the underlying molecular mechanisms in different risk subgroups were also explored via The Cancer Genome Atlas (TCGA) Pan-Cancer study. Results: The glycolysis risk score (GRS) outperformed conventional clinicopathological features for recurrence-free survival prediction. The GRS model identified four candidate genes (ADM, MKI67, CD44 and TYMS), and an accurate predictive model of relapse in DTC patients was established that was highly correlated with prognosis (AUC of 0.767). In vitro assays revealed that high expression of those genes increased DTC cancer cell viability and invasion. Functional enrichment analysis indicated that these signature GRGs are involved in remodelling the tumour microenvironment, which has been demonstrated in pan-cancers. Finally, we generated an integrated decision tree and nomogram based on the GRS model and clinicopathological features to optimize risk stratification (AUC of the composite model was 0.815). Conclusions: The GRG signature-based predictive model may help clinicians provide a prognosis for DTC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.


Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Biomarkers, Tumor/genetics , Glycolysis/genetics , Humans , Neoplasm Recurrence, Local/genetics , Prognosis , Retrospective Studies , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Tumor Microenvironment
2.
Int J Endocrinol ; 2021: 6621067, 2021.
Article in English | MEDLINE | ID: mdl-34306071

ABSTRACT

The health problems caused by the frequent relapse of papillary thyroid carcinoma (PTC) remain a worldwide concern since the morbidity rate of PTC ranks the highest among thyroid cancers. Residues from contralateral central lymph node metastases (con-CLNM) are the key reason for persistence or recurrence of unilateral papillary thyroid carcinoma (uni-PTC); however, the ability to assess the status of con-CLNM in uni-PTC patients is limited. To clarify the risk factors of con-CLNM, a total of 250 patients with uni-PTC who underwent total thyroidectomy and bilateral central lymph node dissection were recruited in this study. We compared the clinical, sonographic, and pathological characteristics of patients with con-CLNM to those without con-CLNM and established a nomogram for con-CLNM in uni-PTC. We found that male sex, without Hashimoto's thyroiditis, present capsular invasion, with ipsilateral lateral lymph node metastases, and the ratio of ipsilateral central lymph node metastases ≥0.16 were independent con-CLNM predictors of uni-PTC (ORs: 2.797, 0.430, 2.538, 2.202, and 26.588; 95% CIs: 1.182-6.617, 0.211-0.876, 1.223-5.267, 1.064-4.557, and 7.596-93.069, respectively). Additionally, a preoperative nomogram for the prediction of con-CLNM based on these risk factors showed good discrimination (C-index 0.881; 95% CI: 0.840-0.923; sensitivity 85.3%; specificity 76.0%) and good agreement via the calibration plot. Our study provided a way to quantitatively and accurately predict whether con-CLNM occurred in patients with uni-PTC, which may guide surgeons to evaluate the nodal status and perform tailored therapeutic central lymph node dissection.

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