Department of Surgery Teaching, Wroclaw Medical University, Wroclaw, Poland.
Department of Genetics, Wroclaw Medical University, Wroclaw, Poland;
Cancer Genomics Proteomics. 2022 Jul-Aug;19(4):503-511. doi: 10.21873/cgp.20336.
The stage of colorectal cancer (CRC) at the day of diagnosis has the greatest influence on survival rate. Thus, for CRC, which is mainly identified as advanced disease, non-invasive, molecular blood or stool tests could boost the diagnosis and lower mortality. Evaluation of miRNA expression levels in serum of patients diagnosed with CRC is a potential tool in early screening. Screening can be supported by machine learning (ML) as a tool for developing a cancer risk predictive model based on genetic data.
miRNA was isolated from the serum of 8 patients diagnosed with CRC and 10 patients from a control group matched for age and sex. The expression of 179 miRNAs was determined using a serum/plasma panel (Exiqon). Determinations were conducted using real-time PCR technique on an Applied Biosystems QuantStudio3 device in 96-well plates. A predictive model was developed through the Azure Machine Learning platform.
A wide panel of 29 up-regulated miRNAs in CRC were identified and divided into two subgroups: 1) miRNAs with significantly higher serum level in cancer patients vs. controls (24 miRNAs) and 2) miRNAs detected only in cancer patients and not in controls (5 miRNAs). Re-analysis of published miRNA profiles of CRC tumours or CRC exosomes revealed that only 2 out of 29 miRNAs were up-regulated in all datasets including ours (miR-34a and miR-25-3p).
Our research suggests the potential role of overexpressed miRNAs as diagnostic or prognostic biomarkers among CRC patients. Such clustering of miRNAs may be a potential direction for discovering new diagnostic panels of cancer (including CRC), especially using ML. The low correspondence between deregulation of miRNAs in serum and tumour tissue revealed in our study confirms previously published reports.
结直肠癌(CRC)在诊断当天的分期对生存率的影响最大。因此,对于主要被诊断为晚期疾病的 CRC,非侵入性、分子血液或粪便检测可以提高诊断率并降低死亡率。评估诊断为 CRC 患者血清中的 miRNA 表达水平是早期筛查的潜在工具。筛查可以通过机器学习(ML)来支持,作为一种基于遗传数据开发癌症风险预测模型的工具。
从 8 名诊断为 CRC 的患者和 10 名年龄和性别匹配的对照组患者的血清中分离 miRNA。使用血清/血浆面板(Exiqon)测定 179 种 miRNA 的表达。使用实时 PCR 技术在 Applied Biosystems QuantStudio3 设备上的 96 孔板中进行测定。通过 Azure 机器学习平台开发预测模型。
鉴定出 CRC 中 29 种上调的 miRNA 的广泛面板,并分为两个亚组:1)癌症患者血清中 miRNA 水平明显高于对照组的(24 个 miRNA)和 2)仅在癌症患者中检测到而不在对照组中检测到的 miRNA(5 个 miRNA)。对已发表的 CRC 肿瘤或 CRC 外泌体 miRNA 图谱的重新分析表明,在包括我们在内的所有数据集(miR-34a 和 miR-25-3p)中,只有 2 种 miRNA 上调。
我们的研究表明,过表达的 miRNA 作为 CRC 患者的诊断或预后生物标志物具有潜在作用。这种 miRNA 的聚类可能是发现癌症(包括 CRC)新诊断面板的潜在方向,特别是使用 ML。我们研究中发现血清和肿瘤组织中 miRNA 失调的低对应性证实了之前的报道。