Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer
Circulating miR-210 as a Novel Hypoxia Marker in Pancreatic Cancer
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DOI：
10.1593/tlo.09256
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Koong, Albert C.
中科院分区：
文献类型：
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作者：
Ho, Allen S.;Huang, Xin;Koong, Albert C.
MicroRNA是一种小的非编码转录物，参与许多细胞机制，包括肿瘤发生。特别是，miR-210是由缺氧诱导的，并与某些癌症的不良结局相关。由于胰腺腺癌表现出极度缺氧的特征，我们假设miR-210可能作为筛查或监测胰腺癌的诊断标志物。血浆样本来自新诊断的胰腺癌患者和年龄匹配的非癌症对照。直接从血浆中提取miRNA并将其逆转录为互补DNA。加入已知数量的合成秀丽隐杆线虫miR-54（细胞-miR-54）进行归一化。然后使用定量逆转录聚合酶链反应测定miR-210和cell - mir -54。本研究采用11例胰腺癌患者和14例年龄匹配的对照作为试验组，11例胰腺癌患者和11例对照作为验证组。miR-210的检测和定量是可靠的，在测试集中，胰腺癌患者中miR-210的表达比正常对照组增加了4倍，具有统计学意义（P < 0.00004）。验证组证实了这一差异（P < 0.018）。总之，胰腺癌患者的循环miR-210水平升高，可能作为胰腺癌诊断的有用生物标志物。
MicroRNA are small noncoding transcripts involved in many cellular mechanisms, including tumorigenesis. miR-210, in particular, is induced by hypoxia and correlates with adverse outcomes in certain cancers. Because pancreatic adenocarcinomas exhibit extremely hypoxic signatures, we hypothesized that miR-210 may serve as a diagnostic marker for screening or surveillance for pancreatic cancer. Plasma samples were obtained from newly diagnosed pancreatic cancer patients and age-matched noncancer controls. miRNA was extracted directly from plasma and reverse-transcribed to complementary DNA. A known quantity of synthetic Caenorhabditis elegans miR-54 (cel-miR-54) was added for normalization. miR-210 and cel-miR-54 were then measured using quantitative reverse transcription polymerase chain reaction. An initial cohort of 11 pancreatic cancer patients and 14 age-matched controls was used as the test set and a second cohort of 11 pancreatic cancer patients and 11 controls was used as the validating set in this study. miR-210 was reliably detected and quantified, with a statistically significant four-fold increase in expression in pancreatic cancer patients compared with normal controls (P < .00004) in the test set. This difference was confirmed in the validation group (P < .018). In summary, circulating miR-210 levels are elevated in pancreatic cancer patients and may potentially serve as a useful biomarker for pancreatic cancer diagnosis.