Identification of a Gene Signature of Cancer-Associated Fibroblasts to Predict Prognosis in Ovarian Cancer.

Abstract

Ovarian cancer (OvCa) is one of the most widespread malignant tumors, which has the highest morbidity and unsatisfactory clinical outcomes among all gynecological malignancies in the world. Previous studies found that cancer-associated fibroblasts (CAFs) play significant roles in tumor growth, progression, and chemoresistance. In the current research, weighted gene co-expression network analysis (WGCNA), univariable COX regression, and the least absolute shrinkage and selection operator (LASSO) analysis were applied to recognize CAF-specific genes. After multiple bioinformatic analyses, four genes (AXL, GPR176, ITGBL1, and TIMP3) were identified as OvCa-specific CAF markers and used to construct the prognostic signature (CAFRS). Furthermore, the specificity of the four genes' expression was further validated at the single-cell level, which was high-selectively expressed in CAFs. In addition, our results showed that CAFRS is an independent significant risk factor affecting the clinical outcomes of OvCa patients. Meanwhile, patients with higher CAFRS were more likely to establish chemoresistance to platinum. Besides, the CAFRS were notably correlated with well-known signal pathways that were related to tumor progression. In summary, our study identifies four CAF-specific genes and constructs a novel prognostic signature, which may provide more insights into precise prognostic assessment in OvCa.