Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC

Abstract Background Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on the molecular heterogeneity of HNSCC is esse...

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Main Authors: Xiaoqin Luo, Chao Li, Gang Qin
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Hereditas
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Online Access:https://doi.org/10.1186/s41065-025-00380-0
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author Xiaoqin Luo
Chao Li
Gang Qin
author_facet Xiaoqin Luo
Chao Li
Gang Qin
author_sort Xiaoqin Luo
collection DOAJ
description Abstract Background Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on the molecular heterogeneity of HNSCC is essential to enhance therapeutic efficacy and prognosis. Methods We integrated four HNSCC datasets (TCGA-HNSCC, GSE27020, GSE41613, and GSE65858) from TCGA and GEO databases. Using 10 multi-omics consensus clustering algorithms via the MOVICS package, we identified two molecular subtypes (CS1 and CS2) and validated their stability. A machine learning-driven prognostic signature was constructed by combining 101 algorithms, ultimately selecting 30 prognosis-related genes (PRGs) with the Elastic Net model. This signature was further linked to immune infiltration, functional pathways, and therapeutic sensitivity. Results CS1 exhibited superior survival outcomes in both TCGA and META-HNSCC cohorts. The PRG-based signature stratified patients into low- and high-risk groups, with the low-risk group showing prolonged survival, enhanced immune cell infiltration (B cells, T cells, monocytes), and activated immune functions (cytolytic activity, T cell co-stimulation). High-risk patients were more sensitive to radiotherapy and chemotherapy (e.g., Cisplatin, 5-Fluorouracil), while low-risk patients responded better to immunotherapy and targeted therapies. Conclusion Our study delineates two molecular subtypes of HNSCC and establishes a robust prognostic model using multi-omics data and machine learning. These findings provide a framework for personalized treatment selection, offering clinical insights to optimize therapeutic strategies for HNSCC patients.
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spelling doaj-art-ec04fb2bc30d456b93e90972e49335482025-02-09T12:40:02ZengBMCHereditas1601-52232025-02-01162112110.1186/s41065-025-00380-0Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCCXiaoqin Luo0Chao Li1Gang Qin2Department of Otolaryngology, University of Electronic Science and Technology of ChinaDepartment of Otolaryngology, University of Electronic Science and Technology of ChinaDepartment of Otolaryngology, The Affiliated Hospital, Southwest Medical UniversityAbstract Background Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on the molecular heterogeneity of HNSCC is essential to enhance therapeutic efficacy and prognosis. Methods We integrated four HNSCC datasets (TCGA-HNSCC, GSE27020, GSE41613, and GSE65858) from TCGA and GEO databases. Using 10 multi-omics consensus clustering algorithms via the MOVICS package, we identified two molecular subtypes (CS1 and CS2) and validated their stability. A machine learning-driven prognostic signature was constructed by combining 101 algorithms, ultimately selecting 30 prognosis-related genes (PRGs) with the Elastic Net model. This signature was further linked to immune infiltration, functional pathways, and therapeutic sensitivity. Results CS1 exhibited superior survival outcomes in both TCGA and META-HNSCC cohorts. The PRG-based signature stratified patients into low- and high-risk groups, with the low-risk group showing prolonged survival, enhanced immune cell infiltration (B cells, T cells, monocytes), and activated immune functions (cytolytic activity, T cell co-stimulation). High-risk patients were more sensitive to radiotherapy and chemotherapy (e.g., Cisplatin, 5-Fluorouracil), while low-risk patients responded better to immunotherapy and targeted therapies. Conclusion Our study delineates two molecular subtypes of HNSCC and establishes a robust prognostic model using multi-omics data and machine learning. These findings provide a framework for personalized treatment selection, offering clinical insights to optimize therapeutic strategies for HNSCC patients.https://doi.org/10.1186/s41065-025-00380-0Head and neck squamous cell carcinomaMulti-omics analysesMachine learningPrognostic modelImmunotherapy
spellingShingle Xiaoqin Luo
Chao Li
Gang Qin
Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
Hereditas
Head and neck squamous cell carcinoma
Multi-omics analyses
Machine learning
Prognostic model
Immunotherapy
title Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
title_full Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
title_fullStr Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
title_full_unstemmed Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
title_short Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC
title_sort multiple machine learning based integrations of multi omics data to identify molecular subtypes and construct a prognostic model for hnscc
topic Head and neck squamous cell carcinoma
Multi-omics analyses
Machine learning
Prognostic model
Immunotherapy
url https://doi.org/10.1186/s41065-025-00380-0
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AT chaoli multiplemachinelearningbasedintegrationsofmultiomicsdatatoidentifymolecularsubtypesandconstructaprognosticmodelforhnscc
AT gangqin multiplemachinelearningbasedintegrationsofmultiomicsdatatoidentifymolecularsubtypesandconstructaprognosticmodelforhnscc