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Identification of microRNAs as blood-based markers for colorectal cancer

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Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States, with estimated 51,370 deaths in 2010 according to NCI. Even though the 5-year death rate of CRC has declined over the past three decades, further progress has been hindered by suboptimal compliance with strategies that can prevent and detect CRC in its early stages, monitor disease progression and predict therapy outcome. Thus, development of non- invasive, simple but accurate tests is needed. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression through non-perfect base-pairing. Recently, accumulating evidence has indicated that aberrant expression of miRNAs is associated with cancer development and progression. The use of circulating miRNAs as biomarkers has begun to be investigated and published in a few studies. A successful blood test would be a major help in deciding on neoadjuvant or adjuvant chemotherapy, and would also be used to follow patients for recurrence after curative resection and after chemotherapy for response. In a pilot study, using TaqMan qRT-PCR based miRNA assays we compared expression of 5 selected miRNAs in a cohort of 85 plasma samples from healthy donors, CRC patients with localized disease, and CRC patients with distant metastatic disease. Our preliminary data showed that all of these miRNAs can be detected in the plasma. Further, the levels of miR-141, a member of the miR-200 family, were significantly elevated in plasma samples from patients with distant metastatic colorectal cancer. Our preliminary data support our hypothesis that specific miRNAs can be used as non-invasive, blood-based markers for early detection, stage stratification and prediction of prognosis in CRC. Our overall objective is to identify and put into routine usage a set of robust plasma miRNA markers for CRC early detection, monitoring early metastasis and evaluating prognosis. PUBLIC HEALTH RELEVANCE: Although the search for plasma markers for cancer is a well-established concept, the finding of markers that are clinically useful is very infrequent. Any marker with favorable performance characteristics would favorably impact cancer screening and monitoring and contribute to improved survival of patients. Therefore, the search for plasma markers for colon cancer in this proposal is critically important.
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