Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Cancer Med. 2024 Apr;13(7):e7117. doi: 10.1002/cam4.7117.
In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC.
We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR-1470 in healthy volunteers and CRC patients were analyzed using qRT-PCR. To evaluate the diagnostic potential of the selected miR-1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR-1470 in CRC cell lines, we detected the miR-1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR-1470 in SW480, HCT-116 cells.
Exosomal miR-1470 exhibited significant up-regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876-0.7920) for exosomal miR-1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR-1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR-1470 in CRC cell lines. CCK8 proliferation assay showed that miR-1470 promoted the proliferation ability of SW480 and HCT-116 cells. Transwell assay showed that miR-1470 promoted the migration and invasion ability of SW480 and HCT-116 cells.
This suggested that non-invasive diagnosis of CRC is possible by detecting the level of miR-1470 in exosomes, which has important implications for early detection and treatment of this disease.
近年来，结直肠癌缺乏特异性诊断标志物，导致其发病率和死亡率呈上升趋势。因此，迫切需要寻找有助于早期癌症检测的分子生物标志物。本研究旨在鉴定结直肠癌细胞外体中具有诊断潜力的特异性微小 RNA（miRNA）。
我们使用结直肠癌细胞外体数据集 GSE39833 筛选差异表达的 miRNA。为了验证公共数据库中的结果，我们收集了 168 例结直肠癌患者和 168 例健康志愿者的血清。使用 qRT-PCR 分析健康志愿者和结直肠癌患者中外泌体 miR-1470 的表达水平。为了评估所选 miR-1470 在区分结直肠癌患者和健康对照者方面的诊断潜力，我们分析了其受试者工作特征曲线。为了探索 miR-1470 在结直肠癌细胞系中的生物学功能，我们在 SW480、HCT-116 细胞中转染 miR-1470 后，通过 CCK8、transwell 等实验检测 miR-1470 对 CRC 细胞生长和转移的调节作用。
与健康志愿者相比，结直肠癌患者的外泌体 miR-1470 表达显著上调。ROC 曲线分析显示外泌体 miR-1470 的曲线下面积（AUC）为 0.74（95%置信区间：0.6876-0.7920），表明其具有作为诊断生物标志物的潜力。此外，CRC 患者 miR-1470 的表达水平与年龄、转移和 HDL 含量相关。我们在结直肠癌细胞系中过表达 miR-1470。CCK8 增殖实验表明 miR-1470 促进了 SW480 和 HCT-116 细胞的增殖能力。transwell 实验表明 miR-1470 促进了 SW480 和 HCT-116 细胞的迁移和侵袭能力。
这表明通过检测外泌体中 miR-1470 的水平可以实现结直肠癌的非侵入性诊断，这对于早期发现和治疗结直肠癌具有重要意义。
