ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1536270
Identification of novel prognostic biomarkers for thyroid cancer by integrated transcriptome analysis of metastasis-associated genes
Provisionally accepted
Bushra AlnwisserSalman Alshehri
Amal Qattan,Ph.D.
Minjing Zou
Abdelilah Aboussekhra
Ali Alzahrani
Yufei Shi*- King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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Distant metastasis (DM) is the most important prognostic factor affecting overall survival (OS) of thyroid cancer. The current study aimed to discover prognostic biomarkers to predict thyroid cancer survival, particularly PTC, the most common subtype of thyroid cancer. Four RNA-seq datasets of experimental lung metastasis from 4 transgenic mouse models of PTC, follicular thyroid cancer (FTC), poorly-differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) were integrated to screen for candidate genes involved in DM. TCGA-THCA dataset were used to validate the candidate genes. A total of 105 up-regulated and 25 down-regulated differentially expressed genes (DEGs) were identified to be present in all 4 datasets. Regulation of cytokine production, inflammation, immune checkpoint regulation, MAPK/ERK cascade were major enriched pathways in metastatic tumor cells. We identified 7 genes whose overexpression was present in 63 of 498 PTC patients (13%) and was associated with poor OS (p<0.01). Clinically, the 7-gene expression signature was associated with older age at the diagnosis, late stage of tumor, tall-cell variant, and higher aneuploidy and hypoxia score.Mutation load was increased in patients with 7-gene expression signature: 26 samples had more than one driver mutations (47%, 26/55). Deep deletions in other chromosomal locus were frequently found in patients with BRAFV600E mutations. In contrast, only 7% patients without 7-gene expression signature had more than one driver mutations (24/243). Increased chromosomal instability were also observed in patients with 7-gene expression signature. We conclude that the 7-gene expression signature is associated with poor prognosis and chromosomal instability. These genes may be useful biomarkers for risk stratification for DM and help decision-making in initial surgical recommendations.
Keywords: Metastasis-associated gene, prognosis, biomarker, metastasis, thyroid cancer 2860, 74 references, 6 figures, 3 Tables
Received: 28 Nov 2024; Accepted: 13 Jan 2025.
Copyright: © 2025 Alnwisser, Alshehri, Qattan,Ph.D., Zou, Aboussekhra, Alzahrani and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yufei Shi, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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