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循环微小RNA作为结直肠癌潜在预后标志物的适用性

Suitability of circulating miRNAs as potential prognostic markers in colorectal cancer.

作者信息

Ristau Jonas, Staffa Jürgen, Schrotz-King Petra, Gigic Biljana, Makar Karen W, Hoffmeister Michael, Brenner Herrmann, Ulrich Alexis, Schneider Martin, Ulrich Cornelia M, Habermann Nina

机构信息

Division of Preventive Oncology, National Center for Tumor Diseases, Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany.

Fred Hutchinson Cancer Research Center, Seattle, Washington.

出版信息

Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2632-7. doi: 10.1158/1055-9965.EPI-14-0556.

Abstract

miRNAs are crucial in cellular processes and have been shown to be abnormally expressed in cancer tissue and the circulation. Circulating miRNAs may serve as a novel class of minimally invasive biomarkers for prognosis. Within a first methodologic study, we evaluated the miRNA profile kinetics in the plasma of patients with colorectal cancer after surgical tumor removal to identify potential suitability as prognostic biomarkers. This pilot study is based on the ColoCare Study, a cohort study of newly diagnosed patients with stage I-IV colorectal cancer. Colorectal cancer pre- and postsurgical blood (2-7 days after surgery) and 6 months follow-up blood from 35 patients were examined and candidate miRNAs were investigated in the plasma. miRNA levels were measured by two-step qRT-PCR. Statistical analysis was performed using log-transformed normalized CT values using SAS 9.3. Comparing pre- and postsurgical miRNA levels revealed a statistically significant decrease of nine circulating miRNAs after surgery (miR92a, miR18a, miR320a, miR106a, miR16-2, miR20a, miR223, miR17, and miR143). Analyses of plasma levels over all three time points demonstrated a statistically significant decrease from presurgery to postsurgery and re-increase from postsurgery to the six months follow-up time point of four circulating miRNAs (miR92a, miR320a, miR106a, and miR18a). We were able to show for the first time that in plasma miRNA profiles change within days after colorectal cancer surgery. Our results underscore the role of the investigated miRNAs in colorectal cancer and their potential utility as prognostic biomarkers. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."

摘要

微小RNA(miRNAs)在细胞过程中至关重要,并且已证实在癌症组织和循环系统中存在异常表达。循环miRNAs可能作为一类新型的微创预后生物标志物。在第一项方法学研究中,我们评估了手术切除肿瘤后结直肠癌患者血浆中的miRNA谱动力学,以确定其作为预后生物标志物的潜在适用性。这项初步研究基于ColoCare研究,这是一项对新诊断的I-IV期结直肠癌患者的队列研究。对35例患者手术前后(术后2-7天)及6个月随访时的血液进行了检查,并对血浆中的候选miRNAs进行了研究。通过两步qRT-PCR测量miRNA水平。使用SAS 9.3对经对数转换的标准化CT值进行统计分析。比较手术前后的miRNA水平发现,术后有9种循环miRNAs出现统计学显著下降(miR92a、miR18a、miR320a、miR106a、miR16-2、miR20a、miR223、miR17和miR143)。对所有三个时间点的血浆水平分析表明,从术前到术后,4种循环miRNAs(miR92a、miR320a、miR106a和miR18a)出现统计学显著下降,从术后到6个月随访时间点又重新升高。我们首次证明,结直肠癌手术后数天内血浆miRNA谱会发生变化。我们的结果强调了所研究的miRNAs在结直肠癌中的作用及其作为预后生物标志物的潜在效用。请参阅本CEBP焦点部分的所有文章,“分子流行病学中的生物标志物;生物标本和新技术”。

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