Integrative Multi-Omics Analysis Reveals Key Metabolic Regulators and Prognostic Biomarkers in Pediatric and Adult Thyroid Cancer

Bin Ling; Mengran Tian; Jinmiao Wang; Wei Luo; Jialong Yu; Xing Wan; Qiman Dong; Ming Gao; Min Zhao; Xiangqian Zheng; Xianhui Ruan

doi:10.7150/jca.117034

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Integrative Multi-Omics Analysis Reveals Key Metabolic Regulators and Prognostic Biomarkers in Pediatric and Adult Thyroid Cancer

Journal article

Open access

Peer reviewed

Integrative Multi-Omics Analysis Reveals Key Metabolic Regulators and Prognostic Biomarkers in Pediatric and Adult Thyroid Cancer

Bin Ling, Mengran Tian, Jinmiao Wang, Wei Luo, Jialong Yu, Xing Wan, Qiman Dong, Ming Gao, Min Zhao, Xiangqian Zheng, …

Journal of Cancer, Vol.16(11), pp.3551-3566

2025

DOI: https://doi.org/10.7150/jca.117034

Appears in Cancer Research Cluster Research Collection

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Abstract

multi-omics integration

thyroid carcinoma (TC)

proteomics

metabolomics

RNA sequencing (RNAseq)

energey metabolism

immunotherapy

Thyroid cancer, including papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC), exhibits distinct molecular characteristics in adult and pediatric populations. Understanding these differences is vital for identifying therapeutic targets and prognostic biomarkers. We performed an integrative multi-omics analysis combining proteomics, phosphoproteomics, metabolomics, and RNA sequencing data from adult and pediatric thyroid cancer cohorts. Differential expression analyses were conducted for all the multi-omics data with false discovery rate adjustments. Enzyme mapping of metabolites was performed using MetaBridge, while cross-omics integration revealed 46 key genes associated with reprogrammed energy metabolism. Clinical relevance was evaluated through survival analyses on cBioPortal and KM plotter platforms, and immunotherapy responses were assessed based on gene expression profiles. The 46 identified genes, primarily involved in mitochondrial energy metabolism and oxidative phosphorylation, were strongly associated with poor disease-free and overall survival in PTC and ATC patients. In ATC, a high tumor mutation burden correlated with worse outcomes, underscoring its prognostic value. Additionally, seven genes (AK2, SUCLG2, NDUFV2, GLUD1, HADHA, ALDH1A1, and NADSYN1) were linked to improved responses to anti-PD-1 immunotherapy, highlighting their potential as biomarkers for treatment stratification. Furthermore, functional studies reveal that AK2 plays a key role in thyroid cancer progression. This study offers critical insights into thyroid cancer biology and provides a foundation for targeted therapies and personalized immunotherapy strategies to improve patient outcomes.

Details

Title: Integrative Multi-Omics Analysis Reveals Key Metabolic Regulators and Prognostic Biomarkers in Pediatric and Adult Thyroid Cancer
Authors: Bin Ling - Tianjin Medical University Cancer Institute and Hospital
Mengran Tian - Nankai University
Jinmiao Wang - Nankai University
Wei Luo - Tianjin Medical University Cancer Institute and Hospital
Jialong Yu - Tianjin Medical University Cancer Institute and Hospital
Xing Wan - Tianjin Medical University Cancer Institute and Hospital
Qiman Dong - Tianjin Medical University Cancer Institute and Hospital
Ming Gao - Nankai University
Min Zhao (Corresponding Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Xiangqian Zheng (Corresponding Author) - Tianjin Medical University Cancer Institute and Hospital
Xianhui Ruan (Corresponding Author) - Tianjin Medical University Cancer Institute and Hospital
Publication details: Journal of Cancer, Vol.16(11), pp.3551-3566
Publisher: Ivyspring International Publisher
Date published: 2025
DOI: 10.7150/jca.117034
ISSN: 1837-9664
Copyright note: This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See https://ivyspring.com/terms for full terms and conditions.
Data Availability: All the data is free to use for academic purposes.
Grant note: This work was supported by the Science &Technology Development Fund of Tianjin Education Commission for Higher Education (2021ZD033)).
Organisation Unit: Cancer Research Cluster; School of Science, Technology and Engineering
Language: English
Record Identifier: 991153711602621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Oncology

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