The First Affiliated Hospital and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Cyrus Tang Medical Institute, State Key Laboratory of Radiation Medicine and Protection, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, National Clinical Research Center for Hematological Diseases, Soochow University, Suzhou, China.
J Clin Lab Anal. 2021 Jun;35(6):e23791. doi: 10.1002/jcla.23791. Epub 2021 May 6.
Tumor-educated platelets (TEPs) may enable blood-based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis.
The TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein-protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real-time PCR (qRT-PCR) was applied to validate the role of DEGs in cancers.
TEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early-stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT-PCR method.
This study suggests that the 7-gene TEPs liquid-biopsy biomarkers may be used for cancer diagnosis and monitoring.
肿瘤衍生血小板（TEPs）可能能够实现基于血液的癌症诊断。本研究旨在鉴定参与致癌作用的诊断性 TEPs 基因。
使用生物信息学方法获取健康样本和早期/晚期癌症样本之间差异表达的 TEPs 基因（DEGs）。通过基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）途径富集分析，鉴定 TEPs DEGs 的途径和功能注释。基于 STRING 数据库分析这些 TEPs DEGs 的蛋白质-蛋白质相互作用，并通过 Cytoscape 软件可视化。进行相关性分析和诊断分析，以评估 TEPs mRNAs 表达对早期/晚期癌症的诊断价值。应用定量实时 PCR（qRT-PCR）验证 DEGs 在癌症中的作用。
TEPs mRNAs 主要参与蛋白质结合、细胞外基质和细胞蛋白质代谢过程。与健康对照相比，RSL24D1 与早期癌症呈负相关，可能具有用于早期癌症诊断的潜力。此外，HPSE、IFI27、LGALS3BP、CRYM、HBD、COL6A3、LAMB2 和 IFITM3 的表达从早期到晚期癌症阶段呈上升趋势。此外，与健康对照相比，ARL2、FCGR2A 和 KLHDC8B 与晚期转移性癌症呈正相关。在 12 个选定的 DEGs 中，包括 RSL24D1、IFI27、CRYM、HBD、IFITM3、FCGR2A 和 KLHDC8B 在内的 7 个 DEGs 的表达通过 qRT-PCR 方法得到验证。
本研究表明，7 个基因的 TEPs 液体活检生物标志物可用于癌症诊断和监测。
