Tissue-derived exosome proteomics identifies promising diagnostic biomarkers for esophageal cancer

• DOI: 10.7554/elife.86209
• Publication Date: 2023-11-15T14:50:07Z
• Authors: Dingyu Rao; Hua Lu; Xiongwei Wang; Zhonghong Lai; Jiali Zhang; Zhixian Tang
• Keywords: Exosome; Cancer Biomarkers; Biomarker Discovery

Esophageal cancer (EC) is a fatal digestive disease with poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed comparative proteomics analysis on paracancer tissue-derived exosomes from eight pairs of patients using label-free quantification profiling analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate candidate plasma-derived in 122 patients. Of 803 discovered exosomes, 686 were up-regulated 117 down-regulated. Intercellular adhesion molecule-1 (CD54) identified as an further investigation, its high expression tissues validated immunohistochemistry, real-time quantitative PCR (RT-qPCR), western blot analyses. In addition, exosome NanoFCM data concurred our proteomic analysis. The receiver operating characteristic (ROC) demonstrated that AUC, sensitivity, specificity values CD54 0.702, 66.13%, 71.31%, respectively, diagnosis. Small interference (si)RNA employed silence gene cells. A series assays, including cell counting kit-8, adhesion, wound healing, Matrigel invasion, investigate viability, adhesive, migratory, invasive abilities, respectively. results showed promoted proliferation, migration, invasion. Collectively, exosomal strongly demonstrates promising biomarker key molecule development.