Ovarian cancer is one of the most common cause of cancer death in women due to its late diagnosis and susceptibility to drug resistance. Adenosine (ADO) signaling plays a key role in immune activity and tumor progression. In this study, we constructed a signature of ADO metabolism related genes expression in patients with ovarian cancer.
A total of 372 ovarian cancer patients from TCGA was used as training set and 1,137 patients from six GEO datasets were as validation set. The gene expression and drug response inhibitory concentration values for ovarian cancer cell line from GDSC were used for drug sensitivity analysis. The non-negative matrix factorization algorithm and ssGSVA were used to construct the ADO score.
Patients with high ADO score had shorter overall survival (OS) than those with low ADO score in both training set (HR = 1.42, 95% CI, 1.06-1.88) and validation sets (pooled HR = 1.24, 95% CI = 1.02-1.51). In GSEA analysis, genes in ATP synthesis related pathways were enriched in the low ADO score group (adjusted P value = 0.02). Further, we observed that the high ADO score group had significantly higher levels of most cancer hallmark signatures (all adjusted P values < 0.01) and T cell dysfunction and exclusion signatures than the low ADO score group (all adjusted P values < 0.001). Patients with lower ADO score tended to be sensitive to common drugs including Olaparib and Paclitaxel (adjusted P values = 0.05 and 0.04, respectively).
In conclusion, the established ADO signature could be used as a prognostic biomarker to stratify ovarian cancer patients and had the potential to guide the drug exploitation and personalized therapy selection.