Data from RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer

Abstract

<div>AbstractPurpose:<p>To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.</p>Experimental Design:<p>RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (<i>n</i> = 5), organoids (<i>n</i> = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery <i>n</i> = 31, validation <i>n</i> = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.</p>Results:<p>RAD51 scores correlated with <i>in vitro</i> response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson <i>r</i> = 0.96, <i>P</i> = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (<i>P</i> < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; <i>P</i> < 0.001) and to be platinum-sensitive (RR, ∞; <i>P</i> = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78–1.0; <i>P</i> < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; <i>P</i> < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33–0.85; <i>P</i> < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25–0.75; <i>P</i> = 0.003) than RAD51-High status.</p>Conclusions:<p>RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.</p></div>

Circulating serum miRNAs predict response to platinum chemotherapy in high-grade serous ovarian cancer

“…Accurate prediction of platinum response is fundamentally important in the clinical management of patients with HGSOC. Previous studies have explored the efficacy of platinum chemotherapy by categorizing patients as those who were platinum-sensitive and those who were platinum-resistant based on a TFIp of 6 months [23,24]. In the present study, we evaluated the expected TFIp before platinum chemotherapy.…”

“…Indicators that might define platinum treatment response in ovarian cancer include TFIp, response rate, and progression-free survival [24,36,37]. Biomarkers that can predict platinum response should be able to predict TFIp in first-line therapy because TFIp is expected.…”