Identification of a cancer associated fibroblasts-related index to predict prognosis and immune landscape in ovarian cancer

Abstract

AbstractCancer-associated fibroblasts (CAFs) play a role in ovarian cancer (OV) evolution, immunosuppression and promotion of drug resistance. Exploring the value of CAFs-related biomarker in OV is of great importance. In the present work, we developed a CAFs-related index (CAFRI) based on an integrated analysis of single-cell and bulk RNA-sequencing and highlighted the value of CAFRI in predicting clinical outcomes in individuals with OV, tumour immune microenvironment (TIME) and response to immune checkpoint inhibitors (ICIs). The GSE151214 cohort was used for cell subpopulation localization and analysis, the TCGA-OV patients as a training set. Moreover, the ICGC-OV, GSE26193, GSE26712 and GSE19829 cohorts were used for the validation of CAFRI. The TIMER 2.0, CIBERSORT and ssGSEA algorithms were used for analysis of TIME characteristics based on the CAFRI. The GSVA, GSEA, GO, KEGG and tumour mutation burden (TMB) analyses were used for mechanistic exploration. Additionally, the IMvigor210 cohort was conducted to validate the predictive value of CAFRI on the efficacy of ICIs. Finally, CAFRI-based antitumour drug sensitivity was analysed. The findings demonstrate that the CAFRI can served as an excellent predictor of prognosis for individuals with OV, as well as identifying patients with different TIME characteristics, differentiating between immune ‘hot’ and ‘cold’ tumour populations, and providing new insights into the selection of ICIs and personalised treatment regimens. CAFRI provides new perspectives for the development of novel prognostic and immunotherapy efficacy predictive biomarkers for OV.