Identification of Potential Tumor-educated Platelets RNA Biomarkers for Pan Cancer Detection and Staging

Abstract

Cancer is a disturbing disease with high morbidity and mortality. Although medical technology has been developed rapidly, diagnosis of cancer is still complicated, difficult, as well as expensive. Furthermore, cancers are mostly diagnosed at an advanced stage. Platelets mRNA profiles are altered after educated by tumors. Thereby, tumor-educated platelets (TEPs) mRNA profiles have the potentially diagnostic value for cancers currently. We downloaded and analyzed the next-generation sequencing datasets, GSE68086 and GSE89843, by integrated bioinformatics. A total of 43 biomarker genes were selected for further pathway enrichment analysis and correlation analysis, as well as diagnostic analysis. Gene ontology (GO) analysis showed these 43 TEPs mRNAs were mostly involved in protein binding, extracellular matrix and cellular protein metabolic process. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that genes were mainly enriched in metabolic process. Eventually, after taking these 43 genes into spearman correlation analysis and receiving operating characteristic (ROC) curve analysis, we identified: 1) TEPs RSL24D1 mRNA was negatively related to early pan cancer as compared to healthy controls, and potential for early pan cancer diagnosis with a sensitivity of 71.8%, and a specificity of 64.3%; 2) HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to more advanced pan cancer stages. The sensitivity of the diagnostic value for pan cancer of these genes was 60.9%, 59.1%, 56.5%, 57.8%, 54.3%, 55.2%, 55.2%, 60.9%, and a specificity of 94.5%, 90.9%, 87.3%, 89.1%, 72.7%, 85.5%, 89.1%, 94.5% respectively; 3) ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic pan cancer as compared to healthy controls and could be diagnostic indicators for advanced pan cancer with a sensitivity of 59.2%, 61.8%, 59.7%, and a specificity of 80%, 89.1%, 83.6%, respectively. In summary, our findings identified that the 12-gene TEP liquid-biopsy biomarkers will not only facilitate early diagnosis of pan cancer, but also be beneficial to pan cancer staging.