Anna Supernat

Impact of clinical factors on accuracy of ovarian cancer detection via platelet RNA profiling

Abstract Ovarian cancer (OC) presents a diagnostic challenge, often resulting in poor patient outcomes. Platelet RNA sequencing, which reflects host response to disease, shows promise for earlier OC detection. This study examines the impact of sex, age, platelet count, and the training on cancer types other than OC on classification accuracy achieved in the previous platelet-alone training data set. A total of 339 samples from healthy donors and 1396 samples from patients with cancer, spanning 18 cancer types (including 135 OC cases) were analyzed. Logistic regression was applied to verify our classifiers’ performance and interpretability. Models were tested at 100% specificity and 100% sensitivity levels. Incorporating patient age as an additional feature along with gene expression increased sensitivity from 68.6% to 72.6%. Models trained on data from both sexes and on female-only data achieved a sensitivity of 68.6% and 74.5%, respectively. Training solely on OC data reduced late-stage sensitivity from 69.1% to 44.1% but increased early-stage sensitivity from 66.7% to 69.7%. This study highlights the potential of platelet RNA profiling for OC detection and the importance of clinical variables in refining classification accuracy. Incorporating age with gene expression data may enhance OC diagnostic accuracy. The inclusion of male samples deteriorates classifier performance. Data from diverse cancer types improves advanced cancer detection but negatively affects early-stage diagnosis.

imPlatelet classifier: image‐converted RNA biomarker profiles enable blood‐based cancer diagnostics

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor‐educated platelets. Here, we developed the imPlatelet classifier, which converts RNA‐sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non‐small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image‐based deep‐learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep‐learning image‐based classifier accurately identifies cancer, even when a limited number of samples are available.