Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer
Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer
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DOI：
10.1016/j.yexmp.2015.12.004
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Hogdall, Estrid
中科院分区：
文献类型：
--
作者：
Jepsen, Rikke Karlin;Novotny, Guy Wayne;Hogdall, Estrid
为了改善结直肠癌 (CRC) 的诊断和风险评估，人们对各种 microRNA (miRNA) 进行了研究。为了阐明 miRNA 分析在 CRC 中的潜力，了解肿瘤内表达水平的异质性至关重要。本研究的目的是评估 CRC 组织中三种选定 miRNA：miR-92a、miR-375 和 miR-424 的肿瘤内方差。材料和方法：对 9 名 CRC 患者的福尔马林固定石蜡包埋组织进行回顾性研究。通过 qRT-PCR 对代表管腔、中央和侵入性边界区的组织进行 miRNA 组织表达水平分析。使用混合模型根据 Delta Delta Cp 值估计方差分量，并以变异系数 (CV) 表示。结果：肿瘤内方差大约是平均肿瘤内 CV 为 56.4%（范围 33.1-77.1%）和平均患者间 CV 为 101.7%（范围 48.8-152.7%）的患者之间观察到的方差的一半。此外，我们发现肿瘤区域之间 miR-92a 和 miR-375 的表达水平存在显着的系统差异，miR-92a 的管腔侵袭差异等于 0.60 Cp（95% CI：030-0.89，p = 0.0003），而 miR-92a 的管腔侵袭差异等于 0.78 Cp（95% CI：0.10-1.46，p = 0.027) 对于 miR-375。结论虽然 miR-92a、miR-375 和 miR-424 的肿瘤内变异很大，但仅占总变异的约 30%。肿瘤区域之间的功能失调可能会导致测量的表达水平的变化，因此了解特定的肿瘤内表达模式对于研究的组织取样以及未来的诊断至关重要。 (C) 2015 Elsevier Inc. 保留所有权利。
Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial.The study aim was to estimate the intra-tumor variance of three selected miRNAs: miR-92a, miR-375 and miR-424 in CRC tissue.Material and methods: A retrospective study on archived formalin-fixed paraffin embedded tissue from 9 patients with CRC. miRNA tissue expression levels were analyzed by qRT-PCR on tissue representing luminal, central and invasive border zones. Variance components were estimated based on Delta Delta Cp values using mixed modeling and presented as coefficients of variation (CV).Results: Intra-tumor variance was approximately half of the variance observed between patients with a mean intra-tumor CV of 56.4% (range 33.1-77.1%) and a mean inter-patient CV of 101.7% (range 48.8-152.7%). Furthermore we found a significant systematic difference in expression levels between tumor zones for miR-92a and miR-375 with a luminal-invasive difference equal to 0.60 Cp (95% CI: 030-0.89, p = 0.0003) for miR-92a and a luminal-invasive difference equal to 0.78 Cp (95% CI: 0.10-1.46, p = 0.027) for miR-375. ConclusionWhile the intra-tumor variance of miR-92a, miR-375 and miR-424 is substantial, it only constitutes approximately 30% of the total variation. Functional deregulation between tumor zones might contribute to variations in measured expression levels, and thus knowledge of specific intra-tumor expression patterns is crucial in tissue sampling for research as well as in future diagnostics. (C) 2015 Elsevier Inc. All rights reserved.