Construction of an aging-related risk signature in high-grade serous ovarian cancer for predicting survival outcome and immunogenicity.

Abstract

Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.