Simultaneous Underexpression of let-7a-5p and let-7f-5p microRNAs in Plasma and Stool Samples from Early Stage Colorectal Carcinoma

Reza Ghanbari, N. Mosakhani, V. Sarhadi, G. Armengol, N. Nouraee, A. Mohammadkhani, S. Khorrami, E. Arefian, M. Paryan, R. Malekzadeh, S. Knuutila
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引用次数: 40

Abstract

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer death worldwide. Early detection of CRC can improve patient survival rates; thus, the identification of noninvasive diagnostic markers is urgently needed. MicroRNAs (miRNAs) have extensive potential to diagnose several diseases, including cancer. In this study, we compared the expression pattern of miRNAs from plasma and stool samples of patients with early stages of CRC (I, II) with that of healthy subjects. We performed miRNA profiling using microarrays on plasma and stool samples of eight patients with CRC and four healthy subjects. Seven miRNAs were found to be underexpressed in both plasma and stool samples of patients with CRC versus healthy subjects. Then, we aimed to verify two out of these seven differentially expressed miRNAs (let-7a-5p and let-7f-5p) by quantitative reverse transcriptase polymerase chain reaction on a larger set of plasma and stool samples of 51 patients with CRC and 26 healthy subjects. We confirmed the results of microarray analysis since their expression was significantly lower in stool and plasma samples of patients with CRC. Moreover, receiver operating characteristic curve analysis demonstrated that fecal let-7f expression levels have significant sensitivity and specificity to distinguish between patients with CRC and healthy subjects. In conclusion, if the results are confirmed in larger series of patients, underexpressed let-7a-5p and let-7f-5p miRNAs in both plasma and stool samples of patients with CRC may serve potentially as noninvasive molecular biomarkers for the early detection of CRC.
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let-7a-5p和let-7f-5p微rna在早期结直肠癌血浆和粪便样本中的同时低表达
结直肠癌(CRC)是世界上第三大最常见的恶性肿瘤和第二大最常见的癌症死亡原因。早期发现结直肠癌可提高患者生存率;因此,迫切需要无创诊断标记物的识别。MicroRNAs (miRNAs)在诊断包括癌症在内的多种疾病方面具有广泛的潜力。在本研究中,我们比较了早期CRC患者(I, II)血浆和粪便样本中mirna的表达模式与健康受试者的表达模式。我们使用微阵列对8名CRC患者和4名健康受试者的血浆和粪便样本进行了miRNA分析。与健康受试者相比,在结直肠癌患者的血浆和粪便样本中发现了7种mirna低表达。然后,我们旨在通过定量逆转录酶聚合酶链反应在51名结直肠癌患者和26名健康受试者的更大血浆和粪便样本上验证这7种差异表达mirna中的2种(let-7a-5p和let-7f-5p)。我们证实了微阵列分析的结果,因为它们在CRC患者的粪便和血浆样本中的表达明显较低。此外,受试者工作特征曲线分析表明,粪便let-7f表达水平对区分结直肠癌患者和健康受试者具有显著的敏感性和特异性。总之,如果结果在更大的患者中得到证实,那么在CRC患者的血浆和粪便样本中表达不足的let-7a-5p和let-7f-5p mirna可能作为CRC早期检测的非侵入性分子生物标志物。
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