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Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma
Author(s) -
Baraniskin Alexander,
NöpelDünnebacke Stefanie,
Ahrens Maike,
Jensen Steffen Grann,
Zöllner Hannah,
Maghnouj Abdelouahid,
Wos Alexandra,
Mayerle Julia,
Munding Johanna,
Kost Dennis,
ReinacherSchick Anke,
Liffers Sven,
Schroers Roland,
Chromik Ansgar M.,
Meyer Helmut E.,
Uhl Waldemar,
KleinScory Susanne,
Weiss Frank U.,
Stephan Christian,
SchwarteWaldhoff Irmgard,
Lerch Markus M.,
Tannapfel Andrea,
Schmiegel Wolff,
Andersen Claus Lindbjerg,
Hahn Stephan A.
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27791
Subject(s) - microrna , rna , biomarker , pancreatic cancer , colorectal cancer , adenocarcinoma , small rna , cancer research , cancer , small nuclear rna , biology , medicine , oncology , pathology , microbiology and biotechnology , gene , non coding rna , genetics
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.