Exosomal MicroRNA: A Diagnostic Marker for Lung Cancer

Exosomal MicroRNA: A Diagnostic Marker for Lung Cancer
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DOI:
10.3816/clc.2009.n.006
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发表时间:
2009-01-01
影响因子:
3.6
通讯作者:
Kloecker, Goetz H.
Kloecker, Goetz H.
中科院分区:
医学3区
文献类型:
--
作者:
Rabinowits, Guilherme;Gercel-Taylor, Cicek;Kloecker, Goetz H.

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目的:到目前为止,没有肺癌筛查试验显示会影响总死亡率。microRNA(miRNAS)是一类在多种癌症中异常表达的小的非编码RNA基因,表明其在人类癌症的发病机制中起作用。患者和方法:我们评估了患有和不患有肺腺癌的患者中肿瘤外泌体、外泌体小RNA和特异性外泌体miRNA的循环水平,将这些水平与美国癌症联合委员会(AJCC)疾病分期相关联,以验证其作为肺腺癌患者诊断和预后的可接受标志物。结果:到目前为止,27例肺腺癌AJCC slage I-IV和9例对照,年龄均为21-80岁,参加了这项研究。在循环外来体中检测到小RNA。肺腺癌组的平均外泌体浓度为2.85 mg/mL(95% CI,1.94-3.76),对照组为0.77 mg/mL(95% CI,0.68-0.86)(P < .001)。肺腺癌组的平均miRNA浓度为158.6 ng/mL(95% CI,145.7-171.5),对照组为68.1 ng/mL(95% CI,57.2-78.9)(P < .001)。外周循环miRNA来源的外来体和miRNA来源的肿瘤之间的比较表明miRNA特征没有显著差异。结论:肺癌患者和对照组之间总外泌体和miRNA水平的显著差异,以及循环外泌体miRNA和肿瘤来源的miRNA模式之间的相似性,表明循环外泌体miRNA可能用作肺腺癌的筛选测试。在这一点上,外泌体miRNA水平与疾病阶段之间没有相关性。
Purpose: To date, there is no screening test for lung cancer shown to affect overall mortality. MicroRNAs (miRNAS) are a class of small noncoding RNA genes found to be abnormally expressed in several types of cancer, suggesting a role in the pathogenesis of human cancer. Patients and Methods: We evaluated the circulating levels of tumor exosomes, exosomal small RNA, and specific exosomal miRNAs in patients with and without lung adenocarcinoma, correlating the levels with the American Joint Committee on Cancer (AJCC) disease stage to validate it as an acceptable marker for diagnosis and prognosis in patients with adenocarcinoma of the lung. Results: To date, 27 patients with lung adenocarcinoma AJCC slages I-IV and 9 controls, all aged 21-80 years, were enrolled in the study. Small RNA was detected in the circulating exosomes. The mean exosome concentration was 2.85 mg/mL (95% CI, 1.94-3.76) for the lung adenocarcinoma group versus 0.77 mg/mL (95% Cl, 0.68-0.86) for the control group (P < .001). The mean miRNA concentration was 158.6 ng/mL (95% Cl, 145.7-171.5) for the lung adenocarcinoma group versus 68.1 ng/mL (95% Cl, 57.2-78.9) for the control group (P < .001). Comparisons between peripheral circulation miRNA-derived exosomes and miRNA-derived tumors indicated that the miRNA signatures were not significantly different. Conclusion: The significant difference in total exosome and miRNA levels between lung cancer patients and controls, and the similarity between the circulating exosomal miRNA and the tumor-derived miRNA patterns, suggest that circulating exosomal miRNA might be useful as a screening test for lung adenocarcinoma. No correlation between the exosomal miRNA levels and the stage of disease can be made at this point.