Anoikis-related signature predicts prognosis and characterizes immune landscape of ovarian cancer

Abstract

Abstract Ovarian cancer (OV) is the most lethal gynecological malignancy worldwide, with high recurrence rates. Anoikis, a newly-acknowledged form of programmed cell death, plays an essential role in cancer progression, though studies focused on prognostic patterns of anoikis in OV are still lacking. We filtered 32 potential anoikis-related genes (ARGs) among the 6406 differentially expressed genes (DEGs) between the 180 normal controls and 376 TCGA-OV samples. Through the LASSO-Cox analysis, a 2-gene prognostic signature, namely AKT2, and DAPK1, was finally distinguished. We then demonstrated the promising prognostic value of the signature through the K-M survival analysis and time-dependent ROC curves (p-value < 0.05). Moreover, based on the signature and clinical features, we constructed and validated a nomogram model for 1-year, 3-year, and 5-year overall survival, with reliable prognostic values in both TCGA-OV training cohort (p-value < 0.001) and ICGC-OV validation cohort (p-value = 0.030). We evaluated the tumor immune landscape through the CIBERSORT algorithm, which indicated the upregulation of resting Myeloid Dendritic Cells (DCs), memory B cells, and naïve B cells and high expression of key immune checkpoint molecules (CD274 and PDCD1LG2) in the high-risk group. Interestingly, the high-risk group exhibited better sensitivity toward immunotherapy and less sensitivity toward chemotherapies, including Cisplatin and Bleomycin. Especially, based on the IHC of tissue microarrays among 125 OV patients at our institution, we reported that aberrant upregulation of DAPK1 was related to poor prognosis. Conclusively, the anoikis-related signature was a promising tool to evaluate prognosis and predict therapy responses, thus assisting decision-making in the realm of OV precision medicine.

Keywords

• Anoikis
• Prognostic signature
• Ovarian cancer
• Immune landscape
• DAPK1