U2 small nuclear RNA as a biomarker in cancer

Abstract

Cancer is the second most common cause of death in western countries today. Despite of modern therapeutic approaches leading to longer survival rates, the only cure for the most solid tumors is resection of the entire tumor. However, cure is generally only possible in patients with limited disease without distant metastases. Therefore, detection of precancerous conditions or early cancer stages is crucial to reduce the mortality of cancer. To date, blood-based biomarkers which can be assayed within the patient’s clinical chemistry workup are the most frequently used markers for detecting cancer. Unfortunately, most of these markers are neither able to detect precancerous conditions nor early cancer stages at the required high sensitivity and specificity levels to be of use in any screening procedure. Recently, RNA fragments derived from the noncoding RNA U2 snRNA were detected at elevated levels among others in the blood of patients suffering from pancreatic, colorectal, and non-small-cell lung cancer as compared to noncancerous controls. Sensitivity and specificity levels reached with the proposed U2 snRNA fragment detection assays were well above the levels reported for current noninvasive blood-based tumor markers used in clinical routine. U2 snRNA fragments proved to be highly stable in the serum and plasma from cancer patients and could be detected by a simple routine PCR-based assay, crucial requirements for an analyte to be successfully implemented into a clinical routine diagnostic procedure. Importantly, the fragments were also found to be significantly elevated in a fraction of early colon and lung cancer patients. Therefore, detection of U2 snRNA fragments in the blood cannot only be regarded as a novel strategy to detect cancer but may also hold promise for detecting some cancer types at a curable stage.