Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
The First Clinical School of Medicine of Southern Medical University, Guangzhou, China.
Elife. 2023 Nov 15;12:e86209. doi: 10.7554/eLife.86209.
Esophageal cancer (EC) is a fatal digestive disease with a poor prognosis and frequent lymphatic metastases. Nevertheless, reliable biomarkers for EC diagnosis are currently unavailable. Accordingly, we have performed a comparative proteomics analysis on cancer and paracancer tissue-derived exosomes from eight pairs of EC patients using label-free quantification proteomics profiling and have analyzed the differentially expressed proteins through bioinformatics. Furthermore, nano-flow cytometry (NanoFCM) was used to validate the candidate proteins from plasma-derived exosomes in 122 EC patients. Of the 803 differentially expressed proteins discovered in cancer and paracancer tissue-derived exosomes, 686 were up-regulated and 117 were down-regulated. Intercellular adhesion molecule-1 (CD54) was identified as an up-regulated candidate for further investigation, and its high expression in cancer tissues of EC patients was validated using immunohistochemistry, real-time quantitative PCR (RT-qPCR), and western blot analyses. In addition, plasma-derived exosome NanoFCM data from 122 EC patients concurred with our proteomic analysis. The receiver operating characteristic (ROC) analysis demonstrated that the AUC, sensitivity, and specificity values for CD54 were 0.702, 66.13%, and 71.31%, respectively, for EC diagnosis. Small interference (si)RNA was employed to silence the CD54 gene in EC cells. A series of assays, including cell counting kit-8, adhesion, wound healing, and Matrigel invasion, were performed to investigate EC viability, adhesive, migratory, and invasive abilities, respectively. The results showed that CD54 promoted EC proliferation, migration, and invasion. Collectively, tissue-derived exosomal proteomics strongly demonstrates that CD54 is a promising biomarker for EC diagnosis and a key molecule for EC development.
食管癌（EC）是一种预后不良且常发生淋巴转移的致命消化道疾病。然而，目前还没有可靠的 EC 诊断生物标志物。因此，我们使用无标记定量蛋白质组学分析方法对 8 对 EC 患者的癌组织和癌旁组织衍生的外泌体进行了比较蛋白质组学分析，并通过生物信息学分析了差异表达蛋白。此外，使用纳米流式细胞术（NanoFCM）验证了来自 122 例 EC 患者血浆衍生外泌体的候选蛋白。在癌组织和癌旁组织衍生的外泌体中发现的 803 个差异表达蛋白中，有 686 个上调，117 个下调。细胞间黏附分子-1（CD54）被鉴定为进一步研究的上调候选物，并用免疫组织化学、实时定量 PCR（RT-qPCR）和 Western blot 分析验证了其在 EC 患者癌组织中的高表达。此外，来自 122 例 EC 患者的血浆衍生外泌体 NanoFCM 数据与我们的蛋白质组学分析一致。受试者工作特征（ROC）分析表明，CD54 对 EC 诊断的 AUC、敏感性和特异性值分别为 0.702、66.13%和 71.31%。采用小干扰（si）RNA 沉默 EC 细胞中的 CD54 基因。进行了一系列实验，包括细胞计数试剂盒-8、黏附、划痕愈合和基质胶侵袭实验，分别研究 EC 细胞活力、黏附、迁移和侵袭能力。结果表明，CD54 促进了 EC 细胞的增殖、迁移和侵袭。综上所述，组织衍生的外泌体蛋白质组学强烈表明 CD54 是 EC 诊断的有前途的生物标志物，也是 EC 发展的关键分子。
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