ABSTRACT
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Subject(s)
Blood Platelets , Ovarian Neoplasms , Humans , Female , Blood Platelets/pathology , Biomarkers, Tumor/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , ChinaABSTRACT
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.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Ovarian Neoplasms , Biomarkers , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , RNAABSTRACT
Individualization of treatment on the basis of in vitro chemosensitivity testing constitutes one of the aims of contemporary oncology Although previous studies report advantages resulting from chemosensitivity laboratory tests, the issue remains an area of interest. The aim of this study was to discuss chemosensitivity assay methods of ovarian cancer cells. ATP-TCA (ATP-based tumor chemosensitivity assay) is the most investigated chemosensitivity test in ovarian cancer with well-documented efficacy Potentially it is possible to use the xCELLigence system to evaluate chemosensitivity of ovarian cancer cells by measuring their colony volume but application of this method remains in the experimental phase. Optimization of ovarian cancer treatment would improve chemotherapy results, thus increasing the overall survival, improving the quality of patient life, decreasing chemotherapy-related toxicity and resulting in economic benefits owing to better drug use.
