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Integrative multi-omics analyses identify molecular subtypes of head and neck squamous cell carcinoma with distinct therapeutic vulnerabilities

ABSTRACT: Integrative multi-omics analyses identify molecular subtypes of head and neck squamous cell carcinoma with distinct therapeutic vulnerabilities

PROVIDER: PRJNA1046117 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26974151_1.fastq.gz	Fastqsanger.gz
	SRR26974151_2.fastq.gz	Fastqsanger.gz
	SRR26974152_1.fastq.gz	Fastqsanger.gz
	SRR26974152_2.fastq.gz	Fastqsanger.gz
	SRR26974153_1.fastq.gz	Fastqsanger.gz

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Integrative multi-omics analyses identify molecular subtypes of head and neck squamous cell carcinoma with distinct therapeutic vulnerabilities

Project description:Substantial heterogeneity in molecular features, patient prognoses, and therapeutic responses in head and neck squamous cell carcinomas (HNSCC) highlights the urgent need to develop molecular classifications that reliably and accurately reflect tumor behavior and inform personalized therapy. Here, we leveraged the similarity network fusion bioinformatics approach to jointly analyze multi-omics datasets spanning copy number variations, somatic mutations, DNA methylation, and transcriptomic profiling and derived a prognostic classification system for HNSCC. The integrative model consistently identified three subgroups (IMC1-3) with specific genomic features, biological characteristics, and clinical outcomes across multiple independent cohorts. The IMC1 subgroup included proliferative, immune-activated tumors and exhibited a more favorable prognosis. The IMC2 subtype harbored activated EGFR signaling and an inflamed tumor microenvironment with cancer-associated fibroblast/vascular infiltrations. Alternatively, the IMC3 group featured highly aberrant metabolic activities and impaired immune infiltration and recruiting. Pharmacogenomics analyses from in silico predictions and from patient-derived xenograft model data unveiled subtype-specific therapeutic vulnerabilities including sensitivity to cisplatin and immunotherapy in IMC1 and EGFR inhibitors (EGFRi) in IMC2, which was experimentally validated in patient-derived organoid models. Two signatures for prognosis and EGFRi sensitivity were developed via machine learning. Together, this integrative multi-omics clustering for HNSCC improves current understanding of tumor heterogeneity and facilitates patient stratification and therapeutic development tailored to molecular vulnerabilities.

2024-06-21 | GSE248855 | GEO

MicroRNA-based subtypes in head and neck squamous cell carcinoma

Project description:MicroRNA-based subtypes in head and neck squamous cell carcinoma

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Head and neck squamous cell carcinoma

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2022-03-01 | PXD001438 | Pride

Molecular Subtypes in Head and Neck Cancer [expression]

2013-03-01 | GSE39366 | GEO

Gene expression profiles of head and neck squamous cell carcinoma

Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue comparative analysis of gene expression profiles of head and neck squamous cell carcinoma and Head and Neck normal tissue

2008-09-30 | E-GEOD-11986 | biostudies-arrayexpress

Molecular Subtypes in Head and Neck Cancer [copy number]

2013-03-01 | GSE39367 | GEO

Molecular Subtypes in Head and Neck Cancer [expression]

Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors. A total of 163 samples were considered. Quality control procedures were applied to microarray probe-level intensity files. A total of 138 tumor arrays remained after removing low-quality arrays, duplicate arrays, and arrays from non-HNSCC samples. The normexp background correction and loess normalization procedures were applied to the probe-level data. After log transformation, probes were matched to a common gene database to produce expression values for 15595 genes.

2013-03-01 | E-GEOD-39366 | biostudies-arrayexpress

Gene expression profiles of head and neck squamous cell carcinoma

Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue

2008-09-30 | GSE11986 | GEO

MicroRNA-based subtypes in head and neck squamous cell carcinoma

Project description:Highly coordinated, deregulated expressions of microRNAs (miRNA) have been implicated in the development of various cancers, including head and neck squamous cell carcinoma (HNSCC). Outside of HPV infection, molecular classification of HNSCC is lacking, and patient stratification by anatomical location and stage does not account for the heterogenous clinical courses seen. Previous studies have proposed molecular classifications based on gene expression, but none describe the role of microRNA expression in HNSCC subtyping. In this study, we identified reliable miRNA clusters that can be used to subclassify HNSCC tumors as well as other squamous tumors of other anatomic locations. An institutional discovery cohort was generated using miRNA expression data from microarrays, and this was validated using publicly available next-generation microRNA sequencing data from TCGA. Further analysis of these subtypes revealed distinct biological and clinical features of HNSCC tumors based on the miRNA expression profiles, which provides new insights into the pathogenesis and treatment of HNSCC.

2020-04-01 | GSE144711 | GEO

Integrative genomic analysis identifies clinically relevant subtypes of head and neck cancer characterized by hypoxia, T-cell infiltration, and EMT

Project description:Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site and clinical stage fails to capture biologic heterogeneity or adequately inform treatment. Here we use consensus clustering on 371 HNSCC in three cohorts, including a new cohort of 134 patients with locoregionally advanced HNSCC and 43% HPV(+) tumors to identify five HNSCC subtypes. Subtypes closely correlate with biologic processes (hypoxia, cytotoxic T-cell infiltration, copy number changes, EGFR/HER-ligand phenotype), survival, and HPV-status. Two biologically distinct HPV-associated subtypes are identified. Gene modules of candidate drivers characterize each subtype using the CONEXIC algorithm. The proposed 5-subtype classification provides a biologic basis for future clinical and preclinical studies and lays the groundwork for improved prognostication and therapy development in HNSCC. We use consensus clustering on 371 HNSCC in three cohorts, including a new cohort of 134 patients with locoregionally advanced HNSCC and 43% HPV(+) tumors to identify five HNSCC subtypes.

2015-03-04 | E-GEOD-40774 | biostudies-arrayexpress

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