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223 A three protein signature fails to externally validate as a biomarker to predict surgical outcome in high grade serous ovarian cancer
  1. A Hawarden1,
  2. M Price2,
  3. G Wilson3,
  4. B Russell2,
  5. L Farrelly4,
  6. A Embleton-Thursk5,
  7. M Parmar5 and
  8. RJ Edmondson1
  1. 1Faculty of Biology, Medicine and Health, University of Manchester and Department of Gynaecological Oncology surgery, Saint Marys Hospital, Manchester University NHS Trust, UK
  2. 2Faculty of Biology, Medicine and Health, University of Manchester, UK
  3. 3Department of Pathology, Manchester University NHS Foundation Trust, UK
  4. 4Cancer Research UK and University College London Cancer Trials Centre, UK
  5. 5MRC Clinical trials Unit, University College London, UK


Introduction Complete cytoreduction is associated with improved survival in patients with advanced High Grade Serous Ovarian Cancer (HGSOC). To aid clinical decision making, many surgical outcome prediction tools have been proposed, but none have been sufficiently validated to warrant routine clinical usage. Here we attempted to externally validate a promising three protein signature, which had shown strong association with suboptimal surgical debulking (AUC 0.89, accuracy 92.8%).

Methods 241 HGSOC tumour samples were collected from patients who participated in a large multicentre trial (ICON5). Samples were collected at the time of initial surgery and before randomisation. Surgical outcome data were collated from the study records. Immunohistochemical scores were generated by two independent observers for the three proteins in the original signature (POSTN, CXCL14 and pSmad2/3). Predictive values were generated for individual and combination protein signatures and as part of a multivariable model using logistic regression.

Results When assessed individually, none of the proteins showed any predictive affinity for suboptimal surgical outcome in our cohort (AUC POSTN 0.55, pSmad 2/3 0.53, CXCL 14 0.62). The combined signature again showed poor predictive ability, AUC 0.58, as did the multivariable model, AUC 0.63.

Conclusion Despite showing original promise, when this protein signature is applied to a large external cohort, it is unable to accurately predictive surgical outcomes. This could be attributed to overfitting of the original model, or differences in surgical practice in our cohort.

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