Dataset Information

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

ABSTRACT:

Objective

The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms.

Design

Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concentrated on the prognostic values of the sex-specific pathways enriched by differentially expressed genes (DEGs) and predicted the potential regulatory mechanisms from immune cell infiltration, ceRNA regulatory network, methylation, and differential coexpression analysis.

Results

Compared with females, males exhibited a lower activity of immune-related functions and higher activities of mitochondrial and ubiquitination functions. The pathway activities were associated with the prognosis of males but less relevant to females. We extracted eight pathways with sex-biased survival patterns, of which five were about down-regulated immune functions, and three were up-regulated pathways (GTP biosynthetic, DNA polymerase, and spliceosomal complex assembly). The five immune pathways were moderately or strongly correlated with the proportion of macrophages. We identified six over-expressed lncRNAs that might be involved in the regulation of the three up-regulated pathways. These lncRNAs exhibited a lower methylation density in males, which might account for their over-expression.

Conclusions

For HNSCCs, males were characterized by immunosuppression. It was a sign of unfavorable prognosis and might be associated the proportion of macrophages. LncRNAs and methylation might be involved in the regulation of these pathways.

SUBMITTER: Wang S

PROVIDER: S-EPMC10102211 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

Wang Shuo S Pan Wei W Mi Wen-Xiang WX Wang Shao-Hai SH

Heliyon 20230328 4

<h4>Objective</h4>The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms.<h4>Design</h4>Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concen ...[more]

PMID: 37064442

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Project description:BackgroundRegional lymph node metastasis is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC) and plays a decisive role in the choice of treatment. Here, we present an independent gene expression validation study of metastasized versus non-metastasized HNSCC.MethodsWe used a dataset recently published by Roepman et al. as reference dataset and an independent gene expression dataset of 11 metastasized and 11 non-metastasized HNSCC tumors as validation dataset. Reference and validation studies were performed on different microarray platforms with different probe sets and probe content. In addition to a supervised gene-based analysis, a supervised pathway-based analysis was performed, evaluating differences in gene expression for predefined tumorigenesis- and metastasis related gene sets.ResultsThe gene-based analysis showed 26 significant differentially expressed genes in the reference dataset, 21 of which were present on the microarray platform used in the validation study. 7 of these genes appeared to be significantly expressed in the validation dataset, but failed to pass the correction for multiple testing. The pathway-based analysis revealed 23 significant differentially expressed gene sets, 7 of which were statistically validated. These gene sets are involved in extracellular matrix remodeling (MMPs, MMP regulating pathways and the uPA system), hypoxia and angiogenesis (HIF1alpha regulated angiogenic factors and HIF1alpha regulated invasion).ConclusionPathways that are differentially expressed between metastasized and non-metastasized HNSCC are involved in the processes of extracellular matrix remodeling, hypoxia and angiogenesis. A supervised pathway-based analysis enhances the understanding of the biological context of the results, the comparability of results across different microarray studies, and reduces multiple testing problems by focusing on a limited number of pathways of interest instead of analyzing the large number of probes available on the microarray.

Dataset Information

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

Objective

Design

Results

Conclusions

Publications

Sex-specific gene expression patterns in head and neck squamous cell carcinomas.

Similar Datasets

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