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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Head and Neck Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1509810
This article is part of the Research Topic Multi-Omics in Head and Neck Cancer: Unveiling Immunological Biomarkers for Therapy View all 4 articles
Multi-omics analysis identifies a liquid-liquid phase separation-related subtypes in head and neck squamous cell carcinoma
Provisionally accepted
Peng-Lei Zhai 1,2* Meng-Min Chen 2,3* Qi Wang 4* Jing-Jun Zhao 1* Xiao-Mei Tang 2,3* Cui-Ni Lu 2,3* Jia Liu 2,3* Qin-Xin Yang 2,3*
Mingliang Xiang 2 Qing-Hai Tang 5* Biao Gu 1* Shu-Ping Zhang 1* Si-Ping Tang 1*
Da Fu 2*- 1 Hengyang Normal University, Hengyang, Hunan Province, China
- 2 Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Beijing, China
- 3 Pancreatic Disease Center, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, China
- 4 Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 5 College of Life Sciences and Environment, Hengyang Normal University, Hengyang, Hunan Province, China
Background: Growing evidence indicates that abnormal liquid-liquid phase separation (LLPS) can disrupt biomolecular condensates, contributing to cancer development and progression. However, the influence of LLPS on the prognosis of head and neck squamous cell carcinoma (HNSCC) patients and its effects on the tumor immune microenvironment (TIME) are not yet fully understood. Therefore, we aimed to categorize patients with HNSCC based on LLPS-related genes and explored their multidimensional heterogeneity.We integrated the transcriptomic data of 3,541 LLPS-related genes to assess the LLPS patterns in 501 patients with HNSCC within The Cancer Genome Atlas cohort.Subsequently, we explored the differences among the three LLPS subtypes using multi-omics analysis. We also developed an LLPS-related prognostic risk signature (LPRS) to facilitate personalized and integrative assessments and then screened and validated potential therapeutic small molecule compounds targeting HNSCC via experimental analyses.Result: By analyzing the expression profiles of 85 scaffolds, 355 regulators, and 3,101 clients of LLPS in HNSCC, we identified three distinct LLPS subtypes: LS1, LS2, and LS3. We confirmed notable differences among these subtypes in terms of prognosis, functional enrichment, genomic alterations, TIME patterns, and responses to immunotherapy.Additionally, we developed the LPRS, a prognostic signature for personalized integrative assessments, which demonstrated strong predictive capability for HNSCC prognosis across multiple cohorts. The LPRS also showed significant correlations with the clinicopathological features and TIME patterns in HNSCC patients. Furthermore, the LPRS effectively predicted responses to immune checkpoint inhibitor therapy and facilitated the screening of potential small-molecule compounds for treating HNSCC patients.This study presents a new classification system for HNSCC patients grounded in LLPS. The LPRS developed in this research offers improved personalized prognosis and could optimize immunotherapy strategies for HNSCC.
Keywords: Liquid-liquid phase separation, Genomic alterations, Tumor immune microenvironment, Immunotherapy, Drug prediction
Received: 11 Oct 2024; Accepted: 11 Feb 2025.
Copyright: © 2025 Zhai, Chen, Wang, Zhao, Tang, Lu, Liu, Yang, Xiang, Tang, Gu, Zhang, Tang and Fu. 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:
Peng-Lei Zhai, Hengyang Normal University, Hengyang, Hunan Province, China
Meng-Min Chen, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Qi Wang, Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
Jing-Jun Zhao, Hengyang Normal University, Hengyang, Hunan Province, China
Xiao-Mei Tang, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Cui-Ni Lu, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Jia Liu, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Qin-Xin Yang, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Qing-Hai Tang, College of Life Sciences and Environment, Hengyang Normal University, Hengyang, 421008, Hunan Province, China
Biao Gu, Hengyang Normal University, Hengyang, Hunan Province, China
Shu-Ping Zhang, Hengyang Normal University, Hengyang, Hunan Province, China
Si-Ping Tang, Hengyang Normal University, Hengyang, Hunan Province, China
Da Fu, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, Beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.