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pmid:34422965

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

Wenlong Wang · Cong Shen · Yunzhe Zhao · Botao Sun · Ning Bai · Xinying Li

Annals of translational medicine · 2021 doi:10.21037/atm-21-383

Paper

complete

Experiment

complete

Data

partial

Analysis

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Identification and validation of potential novel biomarkers to predict distant metastasis in differentiated thyroid cancer.
doi
10.21037/atm-21-383
pmid
34422965
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Wenlong Wang
[1]
Cong Shen
[2]
Yunzhe Zhao
[3]
Botao Sun
[4]
Ning Bai
[5]
Xinying Li
journal
Annals of translational medicine
year
2021
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 co-expressed 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.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34422965", "kind": "science-record", "revision": 7, "content_hash": "sha256:b00bc764fead0d2dfa36f4ecf2a586612adff788fecef6a2ff9407ad9c0f7e6d", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T21:26:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of potential novel biomarkers to predict distant metastasis in differentiated thyroid cancer.", "doi": "10.21037/atm-21-383", "pmid": "34422965", "authors": ["Wenlong Wang", "Cong Shen", "Yunzhe Zhao", "Botao Sun", "Ning Bai", "Xinying Li"], "journal": "Annals of translational medicine", "year": 2021, "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.\nMETHODS: Weighted gene co-expression network analysis (WGCNA) was performed to discover co-expressed 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.\nRESULTS: 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.\nCONCLUSIONS: The present study has provided a reliable model to predict DM in patients with DTC. 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