Integrative Analysis of Bulk Multiomics and Single-Cell Transcriptomics Elucidates Age-Related Molecular Landscape Alterations in Cervical Cancer.

BACKGROUND

Young and elderly patients with cervical cancer represent two distinct demographic cohorts that have attracted considerable attention in clinical practice. However, the age-related molecular characteristics of these groups remain unclear.

METHODS

Data from 307 patients with cervical cancer, including clinical information and comprehensive bulk multiomics data, were obtained from The Cancer Genome Atlas (TCGA). Single-cell RNA-sequencing (scRNA-seq) data for 11 cervical cancer samples were retrieved from the Gene Expression Omnibus (GEO). The patients were stratified into three age groups: young (<30 years), middle (30-64 years), and old (≥65 years). Comparative analyses of survival outcomes, expression profiles, tumor immune microenvironment, genomic and epigenetic features, treatment responsiveness, and cellular composition were performed. Additionally, external validation was performed using bulk transcriptomic and genomic data from the GEO and MSK-IMPACT datasets.

RESULTS

Young patients exhibited a transcriptional landscape characterized by pronounced aggressiveness and elevated expression of immunosuppressive molecules. Conversely, elderly patients exhibited an increased level of genomic instability and mutations accompanied by an elevated tumor mutation burden and neoantigen counts. Notably, the elderly cohort had a lower Tumor Immune Dysfunction and Exclusion (TIDE) score, whereas the young group had a higher radiosensitivity index and reduced imputed sensitivity scores for multiple chemotherapeutic agents. Additionally, scRNA-seq identified epithelial clusters 5 and 9 as subtypes associated with elderly and young patients, respectively, with cluster 5 displaying characteristics resembling cancer stem cells and cluster 9 exhibiting enhanced oncogenic activity and immunosuppressive capabilities.

CONCLUSIONS

Significant molecular disparities were evident among the young, middle-age, and elderly patients. Thus, age-specific management strategies should be considered in cervical cancer treatment.