Abstract
Background
Ovarian cancer (OC) is one of the deadliest malignancies affecting women globally. Anoikis, a critical process that prevents the establishment of detached cells in non-native sites, is closely associated with cancer cell aggressiveness and poor patient outcomes. Despite its significance, research into the prognostic impact of anoikis-related genes (ARGs) in OC remains scant.
Methods
Single-cell RNA sequencing (scRNA-seq) was adopted to analyze anoikis activity using 41 ARGs across diverse cell types. The genomic and clinicopathological data was sourced from GSE26712 project (training cohort) and TCGA-OV project (independent validation set), respectively. Cox regression and the least absolute shrinkage and selection operator (LASSO) technique were utilized to develop an anoikis-related risk score (ANRS) for prognosis evaluation. Additionally, the correlation between ANRS and tumor microenvironment (TME) characteristics was explored. Functional experiments were conducted to elucidate the molecular role of the key gene AP1S2 in OC.
Results
Survival analyses in both cohorts categorized OC patients into two groups based on the median ANRS. The high-ANRS category exhibited evidently worse survival outcomes. Our findings highlighted a strong link between ARGs and TME characteristics, particularly the stromal components, at both bulk and single-cell transcriptomic levels. This underscores the complex interplay between cancer progression and the tumor-promoting stroma. Additionally, AP1S2 knockdown markedly reduced the proliferative and aggressive capabilities of OC cells.
Conclusion
The ANRS-derived prognostic tool offers substantial promise for advancing our understanding of OC progression and assisting gynecologists in developing effective treatment strategies for women suffering from this malignancy.