A Qualitative Transcriptional Signature for Predicting the Recurrence Risk of Prostate Cancer Patients After Radical Prostatectomy

Background: Previously reported transcriptional signatures for predicting the recurrence risk of prostate cancer (PCa) patients after radical prostatectomy are mainly based on risk threshold values of quantitative expression measurements summarized from the signature genes, which are vulnerable to the measurement variation from different experimental batches and the quality of clinical samples. The within-sample relative expression orderings (REOs) of genes, which are the qualitative transcriptional characteristics, are highly robust against batch effects and sample quality variations. Methods: Gene pairs with REOs significantly correlated with the biochemical recurrence free survival (BFS) were identified from 131 PCa samples in the training dataset. A qualitative transcriptional REOs-based signature were selected from these gene pairs . Findings: A signature consisting of 74 gene pairs was developed for predicting the recurrence risk of PCa patients after radical prostatectomy. A sample was assigned as high risk when at least 37 gene pairs voted for high risk; otherwise, low risk. The signature was validated in six independent datasets, including 660 fresh-frozen samples and 106 formalin-fixed paraffin-embedded samples. The Kaplan-Meier survival analysis showed that the average BFS of the low-risk groups were significantly better than that of the high-risk groups. Analyses of multi-omics data of PCa samples from TCGA suggested that both the epigenomic and genomic alternations could cause the reproducible transcriptional differences between the two different prognostic groups. Interpretation: The proposed qualitative transcriptional signature can robustly stratify PCa patients after radical prostatectomy into two groups with different recurrence risk and distinct multi-omics characteristics. Funding Statement: This work was supported by the National Natural Science Foundation of China (Grant Nos: 81602738 and 81872396), young and middle-aged backbone training project in the health system of Fujian province (Grant No. 2017-ZQN-56), outstanding youth scientific research personnel training program in Fujian Province University (Grant No. 2017B018). Declaration of Interests:The authors declare no competing interests. Ethics Approval Statement: Not required.