Abstract A75: Big data and computational biology method for personalized prognosis of high-grade serous ovarian carcinoma.

Abstract

Abstract The field of personalized disease prognosis, risk prediction and disease management has always attracted the attention of scientists and clinicians worldwide. Translating current clinical research and emerging genome-scale molecular biomarkers of ovarian and other cancers is yielding promising new insights into predictive signatures and potential clinical targets, moving treatment in favor of more personalized therapeutic approaches. Integrative genomics, big data analysis and the disease prediction modelling have become the major driving factors in understanding how to reproducibly stop a disease for individual patients - a goal of precision medicine. In clinical practice, prognostic and predictive factors could be measured as continuous or discrete variables. Here, we proposed a novel methodology to predict disease/treatment outcome via analysis of the similarities between any pair of patients who are each characterized by a certain set of pre-defined biological variables (biomarkers or clinical features) represented initially as a prognostic binary variable vector (PBVV) and subsequently transformed to a prognostic signature vector (PSV). High-grade serous ovarian carcinoma (HGSC) is the most prevalent ovarian cancer, and is one of the most lethal gynecological diseases in the world today. Many molecular signatures for prognostic and disease prediction of HGSC have been proposed, but no been implemented in clinical practice yet. In our previous study, the highly-confidence prognostic classifier, comprising 36 mRNAs that can stratify the HGSC patients into low, intermediate or high-risk subgroups with significantly distinct overall survival outcomes and sensitivity to post-surgery chemotherapy, has been proposed [1]. In this work, we used this classifier as the discriminative model of prognosis of HGSC patients. We implemented our methods to personalized prognosis of HGSC patients of TCGA database based on our molecular predictor [1]. Our results revealed that patient's age, when converted into discrete binary values, was positively correlated with the overall risk of succumbing to the disease and can be used as independent prognostic factor. The inclusion of age into the molecular survival predictor provided more robust personalized prognosis of overall survival when applied to an independent testing metadata composing 359 HGSC patients. In summary, we propose that our personalized prognosis methods and results after including age as prognostic factor could provide clinical benefits in the context of personalized prognosis and therapeutic assignment of HGSC patients. Our method can be generalized and implemented in many other diseases to accurately predict personalized patients' outcomes. [1]. Tang Z, Ow GS, Thiery JP, Ivshina AV and Kuznetsov VA. Int J Cancer. 2013; 134(2):306-318. Citation Format: Ghim Siong Ow, Zhiqun Tang, Anna Vladimirovna Ivshina, Vladimir Andreevich Kuznetsov. Big data and computational biology method for personalized prognosis of high-grade serous ovarian carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A75.