A Qualitative Transcriptional Signature for Predicting Recurrence Risk for High-Grade Serous Ovarian Cancer Patients Treated With Platinum-Taxane Adjuvant Chemotherapy

Resistance to platinum and taxane adjuvant chemotherapy (ACT) is the main cause of the recurrence and poor prognosis of high-grade serous ovarian cancer (HGS-OvCa) patients receiving platinum-taxane ACT after surgery. However, currently reported quantitative transcriptional signatures, which are commonly based on risk scores summarized from gene expression, are unsuitable for clinical application because of their high sensitivity to experimental batch effects and quality uncertainties of clinical samples. Using 226 samples of HGS-OvCa patients receiving platinum-taxane ACT in TCGA, we developed a qualitative transcriptional signature, consisting of four gene pairs whose within-samples relative expression orderings could robustly predict patient recurrence-free survival (RFS). In two independent test datasets, the predicted non-responders had significantly shorter RFS than the predicted responders (log-rank p < 0.05). In a test dataset containing data for patient pathological response state, the signature reclassified 12 out of 22 pathological complete response patients as non-responders and two out of 16 pathological non-complete response patients as responders. Notably, the 12 predicted non-responders in the pathological complete response group had significantly shorter RFS than the predicted responders (log-rank p = 0.0122). This qualitative transcriptional signature, which is insensitive to experimental batch effects and quality uncertainties of clinical samples, can individually identify HGS-OvCa patients who are more likely to benefit from platinum-taxane adjuvant chemotherapy.