Doğan Berkcan, Pirim Dilek, Işık Özgen, Evrensel Türkkan
Department of Translational Medicine, Institute of Health Sciences, Bursa Uludag University, Bursa, Türkiye.
Faculty of Medicine, Department of Medical Genetics, Bursa Uludag University, Bursa, Türkiye.
J Clin Lab Anal. 2025 Apr;39(7):e70013. doi: 10.1002/jcla.70013. Epub 2025 Mar 11.
Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Recent studies suggest the promising potential of microRNAs (miRNA) in predicting the status of circulating tumor cells (CTC), and their combined analyses could pave the way for significant advancements in assessing the risk of metastatic cancer. Here, we investigate the circulating miRNA signatures associated with CTC status in metastatic CRC (mCRC).
The CTC status of mCRC patients was assessed using AdnaTest ColonCancer technology, which detects tumor cells using an immunomagnetic approach and characterizes them based on colon-specific surface markers. The miRNA profiles were analyzed using the Agilent miRNA microarray in 8 CTC-positive, 8 CTC-negative, and eight healthy individuals. The functional implications of dysregulated miRNAs and their interactions with target mRNAs, TFs, and lncRNAs were determined through a comprehensive in silico analysis. Candidate miRNAs that were differentially expressed in CTC-positive and CTC-negative groups, which have prior evidence for their role in CRC biology, were validated using qPCR.
We identified two groups of dysregulated miRNAs associated with CTC status and multiple candidate biomarkers in suggested miRNA regulatory networks. Three miRNAs (hsa-miR-199a-5p, hsa-miR-326, hsa-miR-500b-5p), which were downregulated in the CTC-positive group compared to the CTC-negative group, were confirmed by qPCR and prioritized as candidate predictors of CTC status in mCRC.
Our findings suggest biomarker candidates that can be used to predict CTC status in individuals with mCRC. This might also provide new insights into new translational medicine applications in the management of mCRC through miRNA-based CRC-associated CTC detection.
结直肠癌（CRC）是全球第三大常见癌症。最近的研究表明，微小RNA（miRNA）在预测循环肿瘤细胞（CTC）状态方面具有广阔的潜力，其联合分析可为评估转移性癌症风险带来重大进展。在此，我们研究转移性结直肠癌（mCRC）中与CTC状态相关的循环miRNA特征。
使用AdnaTest结肠直肠癌技术评估mCRC患者的CTC状态，该技术采用免疫磁珠法检测肿瘤细胞，并根据结肠特异性表面标志物对其进行表征。在8名CTC阳性、8名CTC阴性和8名健康个体中，使用安捷伦miRNA微阵列分析miRNA谱。通过全面的计算机分析确定失调miRNA的功能意义及其与靶mRNA、转录因子（TF）和长链非编码RNA（lncRNA）的相互作用。在CTC阳性和阴性组中差异表达且先前有证据表明其在CRC生物学中起作用的候选miRNA，使用定量聚合酶链反应（qPCR）进行验证。
我们在建议的miRNA调控网络中鉴定出两组与CTC状态相关的失调miRNA和多个候选生物标志物。与CTC阴性组相比，在CTC阳性组中下调的三种miRNA（hsa-miR-199a-5p、hsa-miR-326、hsa-miR-500b-5p）通过qPCR得到证实，并被优先作为mCRC中CTC状态的候选预测指标。
我们的研究结果表明，有可用于预测mCRC患者CTC状态的候选生物标志物。这也可能为基于miRNA的CRC相关CTC检测在mCRC管理中的新转化医学应用提供新见解。
