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Multi-omics clustering analysis carries out the molecular-specific subtypes of thyroid carcinoma: implicating for the precise treatment strategies

Genes & Immunity volume 26, pages 137–150 (2025)Cite this article

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Abstract

Thyroid cancer (TC) is the most prevalent endocrine malignancy worldwide. This study aimed to explore the molecular subtypes and improve the selection of targeted therapies. We used multi-omics data from 539 patients with DNA methylation, gene mutations, mRNA, lncRNA, and miRNA expressions. This study employed consensus clustering algorithms to identify molecular subtypes and used various bioinformatics tools to analyze genetic alterations, signaling pathways, immune infiltration, and responses to chemotherapy and immunotherapy. Two prognostically relevant TC subtypes, CS1 and CS2, were identified. CS2 was associated with a poorer prognosis of shorter progression-free survival times (P < 0.001). CS1 exhibited higher copy number alterations but a lower tumor mutation burden than CS2. CS2 exhibited activation in cell proliferation and immune-related pathways. Drug sensitivity analysis indicated CS2’s higher sensitivity to cisplatin, doxorubicin, paclitaxel, and sunitinib, whereas CS1 was more sensitive to bicalutamide and FH535. The different activated pathways and sensitivity to drugs for the subtypes were further validated in an external cohort. Twenty-four paired tumors and adjacent normal tissues by immunohistochemical staining further demonstrated the prognostic value of CXCL17. In conclusion, we identified two distinct molecular subtypes of TC with significant implications for prognosis, genetic alterations, pathway activation, and treatment response.

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Fig. 1: Recognition of multi-omics subtypes based on multi-omics data.
Fig. 2: Distinct genetic alterations among multi-omics subtypes.
Fig. 3: Different molecular features and prediction of chemotherapy response.
Fig. 4: Different immunocyte infiltration, sensitivity to immunotherapy, and regulons among multi-omics subtypes and the connections between multi-omics classification and BRAFV600E- RAS classification.
Fig. 5: Different activated signaling pathways among multi-omics subtypes and response to chemotherapy in the GEO-combined cohort.
Fig. 6: CS1 and CS2 subtypes exhibited distinct immunocyte infiltration landscapes and different responses to immunotherapy.
Fig. 7: Dimensionality reduction and molecular typing validation for thyroid carcinoma.
Fig. 8: Clinical validation of CXCL17 expression in thyroid carcinoma.

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Data availability

All data used in this work can be acquired from the GDC portal (https://portal.gdc.cancer.gov/), Gene-Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/).

Code availability

The code generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We appropriate for the developers of the R package “MOVICS”.

Funding

This work was supported by the Research Fund of the Anhui Institute of Translational Medicine (2021zhyx-C30).

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Author notes

  1. These authors contributed equally: Zhenglin Wang, Qijun Han, Xianyu Hu.

Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University Hefei, Hefei, 230022, Anhui, PR China

    Zhenglin Wang, Xianyu Hu, Xu Wang, Rui Sun, Siwei Huang & Wei Chen

  2. Department of interventional radiology, Fuyang People’s Hospital, Fuyang, 236000, Anhui, PR China

    Qijun Han

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Contributions

Conception and Design: Zhenglin Wang, and Wei Chen. Collection and Assembly of Data: Xianyu Hu, Qijun Han and Xu Wang. Data Analysis and Interpretation: Zhenglin Wang, Xianyu Hu, Xu Wang and Rui Sun. Manuscript Writing: Zhenglin Wang, Xianyu Hu, Siwei Huang and Wei Chen. Final Approval of Manuscript: All the authors.

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Correspondence to Wei Chen.

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The current study was approved by Ethics Committee of The First Affiliated Hospital of Anhui Medical University (Quick-PJ2024-03-41). The samples included in our study were surgically removed tissues from patients, and our study was conducted as a retrospective analysis. Since this research did not influence clinical diagnosis or treatment, the ethics committee determined that participant consent could be waived under these circumstances.

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Wang, Z., Han, Q., Hu, X. et al. Multi-omics clustering analysis carries out the molecular-specific subtypes of thyroid carcinoma: implicating for the precise treatment strategies. Genes Immun 26, 137–150 (2025). https://doi.org/10.1038/s41435-025-00322-w

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