Cho Oyeon, Kim Do-Wan, Cheong Jae-Youn
Department of Radiation Oncology, Ajou University School of Medicine, Suwon 16499, Korea.
Ajou Translational Omics Center, Ajou University School of Medicine, Suwon 16499, Korea.
J Clin Med. 2021 May 13;10(10):2110. doi: 10.3390/jcm10102110.
Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log fold change (logFC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as logFC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of and decreased expression of Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. LogFCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts.
血浆外泌体微小RNA（miRNA）是癌症患者中与多种生物学功能相关的细胞间相互作用的关键调节因子。这项初步研究旨在调查宫颈癌患者血液中外泌体miRNA和相关mRNA表达的对数倍变化（logFC），以确定比现有指标更好的预后标志物。我们对28例接受同步放化疗（CCRT）的宫颈癌患者采集的56份血样中的血浆外泌体RNA进行了测序。CCRT前后miRNA和mRNA表达的变化用logFC表示。在选择了两组分别与早期进展（EP）和转移（也称为初始阶段）相关的miRNA后，通过miRNA-mRNA网络分析（使用 Ingenuity Pathway Analysis）研究它们的生物学功能。7例患者出现EP，其中3例在进展后4个月内死亡。EP患者中miR-1228-5p、miR-33a-5p、miR-3200-3p和miR-6815-5p水平降低，miR-146a-3p水平升高，提示炎症未消退，同时 表达增加， 表达降低。miR-605-5p、miR-6791-5p、miR-6780a-5p和miR-6826-5p水平升高，miR-16-1-3p（或15a-3p）水平降低与转移程度相关，并导致髓样细胞、内皮细胞、上皮细胞以及神经元、吞噬细胞和血小板的全身激活。CCRT后血浆外泌体中miRNA和mRNA表达的logFC分别与EP和转移相关，反映了未消退的炎症和全身微环境因素。然而，这项研究得到的初步数据不足以得出明确结论，应在更大的前瞻性队列中进行验证。
