期刊
INTERNATIONAL JOURNAL OF CANCER
卷 132, 期 2, 页码 E48-E57出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.27791
关键词
pancreatic ductal adenocarcinoma; colorectal; carcinoma; hsa-miR-1246; diagnosis; serum; RNU2-1; U2 snRNA
类别
资金
- Bundesministerium fur Bildung und Forschung [01GS08118]
- Deutsche Krebshilfe [70-2988]
- Heinrich und Alma Vogelsang Stiftung, Germany
- Danish National Advanced Technology Foundation [007-2009-2]
- Ministry of Science, North Rhine-Westphalia, Germany [PURE]
- Alfried-Krupp-von-Bohlen-und-Hahlbach-Foundation (Graduate Schools Tumour Biology and Free Radical Biology)
- Deutsche Forschungsgemeinschaft [DFG GRK840-E3/E4], MA 4115/1-2/3, NI 1297/1-1]
- Federal Ministry of Education and Research [BMBF GANI-MED 03152061A, BMBF 0314107]
- European Union [EU-FP-7: EPC-TM, EU-FP7-REGPOT-2010-1]
- Deutsche Krebshilfe/Dr. Mildred-Scheel-Stiftung [109102]
Improved non-invasive strategies for early cancer detection are urgently needed to reduce morbidity and mortality. Non-coding RNAs, such as microRNAs and small nucleolar RNAs, have been proposed as biomarkers for non-invasive cancer diagnosis. Analyzing serum derived from nude mice implanted with primary human pancreatic ductal adenocarcinoma (PDAC), we identified 15 diagnostic microRNA candidates. Of those miR-1246 was selected based on its high abundance in serum of tumor carrying mice. Subsequently, we noted a cross reactivity of the established miR-1246 assays with RNA fragments derived from U2 small nuclear RNA (RNU2-1). Importantly, we found that the assay signal discriminating tumor from controls was derived from U2 small nuclear RNA (snRNA) fragments (RNU2-1f) and not from miR-1246. In addition, we observed a remarkable stability of RNU2-1f in serum and provide experimental evidence that hsa-miR-1246 is likely a pseudo microRNA. In a next step, RNU2-1f was measured by qRT-PCR and normalized to cel-54 in 191 serum/plasma samples from PDAC and colorectal carcinoma (CRC) patients. In comparison to 129 controls, we were able to classify samples as cancerous with a sensitivity and specificity of 97.7% [95% CI = (87.7, 99.9)] and 90.6% [95% CI = (80.7, 96.5)], respectively [area under the ROC curve 0.972]. Of note, patients with CRC were detected with our assay as early as UICC Stage II with a sensitivity of 81%. In conclusion, this is the first report showing that fragments of U2 snRNA are highly stable in serum and plasma and may serve as novel diagnostic biomarker for PDAC and CRC for future prospective screening studies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据