Abstract 1065: Two-step method for early detection of ovarian cancer with high specificity via platelet RNA

Abstract Owing to lack of disease-specific symptoms and screening methods, most of patients with ovarian cancer are diagnosed at an advanced stage. Recent technology based on platelet RNA aids in detection of tumors at the early stages. Also, for population screening of low-prevalence diseases like cancer, accurate detection with high specificity is essential to improve diagnostic methods. Thus, we proposed platelet RNA-based early ovarian cancer detection with great specificity. It is a two-step method for detecting ovarian tumors with more than 99% specificity using exon-exon junction features and sampling invariant normalization and finding their malignancy with more than 99% negative predictive value using exon-exon junction and hematology parameters. First, we downloaded public platelet transcriptome data of gynecological cancer including ovarian cancer (n=151), benign tumor (n=30), and healthy counterparts (n=218) from GEO (GSE158508, 89843, and 183635). Second, we prospectively enrolled patients with gynecological cancer (n=31), benign tumors (n=20), and healthy women (n=18) at Seoul National University Hospital (SNUH) and Boaz Medical Center and obtained platelet transcriptome data (FMH data). Feature selection and model development were conducted using public training set (n=243), public validation set (n=156), and FMH training/validation set (n=47). The batch-invariant normalization was performed, and 198 splice junctions were selected as features from training/validation set for the bootstrap aggregation of the SVM model diagnosing the existence of an ovarian tumor. The model performance was assessed from a separate test set only composed of FMH data (n=22). Our model that demonstrated 96.8% sensitivity, 100.0% specificity, with a predetermined cut-off value. Next, FMH training/validation set was used for model development of following malignancy test. 10 splice junctions and 19 hematology parameters were selected and SVM models were separately developed for splice junctions and hematology parameters using 5-fold cross validation. The predictions were combined using a logical OR operation to obtain the final prediction result. The result showed its diagnostic performance with 100% sensitivity or NPV, and 50.0% specificity in the test data set with a predetermined cut-off value. We proposed a two-step method to operationally improve the existing protocol for ovarian cancer screening. Our model initially excludes most healthy individuals who do not have ovarian tumors and excludes patients with benign ovarian tumors who do not necessitate medical testing. To conclude, our model allows physicians to identify a subset of ovarian tumor patients with a higher risk of malignancy even at early stages; it exhibits potential in enhancing early diagnosis of ovarian cancer, leading to increase of treatment effectiveness and ultimately augmenting the survival of patients with ovarian cancer. Citation Format: Eunyong Ahn, Se Ik Kim, Sungmin Park, Sarah Kim, Yeochan Kim, Eunchong Huang, Suyeon Lee, Dong Won Hwang, Heeyeon Kim, HyunA Jo, Untack Cho, Juwon Lee, TaeJin Ahn, Yong-Sang Song. Two-step method for early detection of ovarian cancer with high specificity via platelet RNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1065.