Suitability of circulating miRNAs as potential prognostic markers in colorectal cancer.
Suitability of circulating miRNAs as potential prognostic markers in colorectal cancer.
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DOI：
10.1158/1055-9965.epi-14-0556
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Habermann N
中科院分区：
文献类型：
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作者：
Ristau J;Staffa J;Schrotz-King P;Gigic B;Makar KW;Hoffmeister M;Brenner H;Ulrich A;Schneider M;Ulrich CM;Habermann N
MicroRNAs （miRNAs）在细胞过程中起着至关重要的作用，并且在肿瘤组织和血液循环中异常表达。循环mirna可能作为一种新型的微创预后生物标志物。在第一项方法学研究中，我们评估了结肠直肠癌（CRC）患者手术切除肿瘤后血浆中的miRNA谱动力学，以确定作为预后生物标志物的潜在适用性。这项试点研究基于ColoCare研究，这是一项针对新诊断的I-IV期CRC患者的队列研究。对35例患者的结直肠癌术前、术后（术后2-7天）血液和6个月随访血液进行检测，并对血浆中的候选mirna进行研究。采用两步qRT-PCR检测miRNA水平。采用SAS 9.3进行对数变换归一化CT值的统计分析。比较术前和术后的miRNA水平显示，术后9种循环miRNA （miR-92a、miR-18a、miR-320a、miR-106a、miR-16-2、miR-20a、miR-223、miR-17、miR-143）水平有统计学意义的降低。所有三个时间点的血浆水平分析显示，四种循环mirna （miR-92a, miR-320a, miR-106a, miR-18a）从手术前到手术后下降，从手术后到6个月随访时间点再次上升，具有统计学意义。我们首次能够证明，在结直肠癌手术后几天内，血浆miRNA谱发生了变化。我们的研究结果强调了所研究的mirna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。
MicroRNAs (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 colorectal cancer (CRC) patients 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 stage I–IV CRC patients. CRC pre- and post-surgical blood (2–7 days after surgery) and six months follow-up blood from n=35 patients was 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 post-surgical miRNA levels revealed a statistically significant decrease of nine circulating miRNAs post surgery (miR-92a, miR-18a, miR-320a, miR-106a, miR-16-2, miR-20a, miR-223, miR-17, miR-143). Analyses of plasma levels over all three time points demonstrated a statistically significant decrease from pre-surgery to post-surgery and re-increase from post-surgery to the six months follow up time point of four circulating miRNAs (miR-92a, miR-320a, miR-106a, miR-18a). We were able to show for the first time that in plasma miRNA profiles change within days after CRC surgery. Our results underscore the role of the investigated miRNAs in CRC and their potential utility as prognostic biomarkers.