Candidate Biomarkers Associated With Circulating Tumor Cell Status in Metastatic Colorectal Cancer

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis Pub Date : 2025-03-11 DOI:10.1002/jcla.70013

Berkcan Doğan, Dilek Pirim, Özgen Işık, Türkkan Evrensel

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Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Abstract Image

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与转移性结直肠癌循环肿瘤细胞状态相关的候选生物标志物

背景：结直肠癌（Colorectal cancer， CRC）是全球第三大常见癌症。最近的研究表明，microrna （miRNA）在预测循环肿瘤细胞（CTC）状态方面具有很大的潜力，它们的联合分析可能为评估转移性癌症的风险铺平道路。在这里，我们研究了与转移性CRC （mCRC）中CTC状态相关的循环miRNA特征。方法：使用AdnaTest ColonCancer技术评估mCRC患者的CTC状态，该技术使用免疫磁性方法检测肿瘤细胞，并基于结肠特异性表面标记物对其进行表征。使用Agilent miRNA微阵列分析8名ctc阳性、8名ctc阴性和8名健康个体的miRNA谱。通过全面的计算机分析确定了失调的mirna及其与靶mrna、tf和lncrna的相互作用的功能意义。使用qPCR验证了在ctc阳性和ctc阴性组中差异表达的候选mirna，这些mirna在CRC生物学中具有先前的作用。结果：我们确定了两组与CTC状态相关的失调miRNA，并在建议的miRNA调节网络中发现了多个候选生物标志物。三个mirna （hsa-miR-199a-5p, hsa-miR-326, hsa-miR-500b-5p）在CTC阳性组中与CTC阴性组相比下调，通过qPCR证实，并优先作为mCRC中CTC状态的候选预测因子。结论：我们的研究结果提示候选生物标志物可用于预测mCRC患者的CTC状态。这也可能为通过基于mirna的crc相关CTC检测在mCRC管理中的新的转化医学应用提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.