RNA sequencing of tumor educated platelets reveals a three-gene diagnostic signature in esophageal squamous cell carcinoma

We aimed to investigate the diagnostic potential of tumor educated platelets in ESCC. In this study, seventy-one ESCC patients and eighty healthy individuals were enrolled and divided into training cohort (23 patients and 27 healthy individuals) and validation cohort (48 patients and 53 healthy individuals). Next-generation RNA sequencing was performed on platelets isolated from peripheral blood of all participants and a support vector machine/leave-one-out cross validation (SVM/LOOCV) approach was used for binary classification. A diagnostic signature composed of ARID1A, GTF2H2 and PRKRIR discriminated ESCC patients from healthy individuals with 91.3% sensitivity and 85.2% specificity in the training cohort and 87.5% sensitivity and 81.1% specificity in the validation cohort. The AUC was 0.924 (95% CI, 0.845–0.956) and 0.893 (95% CI, 0.821–0.966), respectively, in the training cohort and validation cohort. This 3-gene platelet RNA signature could effectively discriminate ESCC from healthy control. Our data highlighted the potential of tumor educated platelets for the noninvasive diagnosis of ESCC. Moreover, we found keratin and collagen protein families, and ECM-related pathways might be involved in tumor progression and metastasis of ESCC, which might provide insights to understand ESCC pathobiology and advance novel therapeutics. Overall design: RNA sequencing of periphral blood platelets in 71 esophagus squemous cell carcinoma patients and 25 healthy controls.