Abstract
BackgroundColorectal cancer (CRC) remains one of the major cancer types and cancer related death worldwide. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer.Methodology/Principal FindingsBy using quantitative reverse transcription-polymerase chain reaction, we found that circulating miR-141 was significantly associated with stage IV colon cancer in a cohort of 102 plasma samples. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of miR-141 and carcinoembryonic antigen (CEA), a widely used marker for CRC, further improved the accuracy of detection. These findings were validated in an independent cohort of 156 plasma samples collected at Tianjin, China. Furthermore, our analysis showed that high levels of plasma miR-141 predicted poor survival in both cohorts and that miR-141 was an independent prognostic factor for advanced colon cancer.Conclusions/SignificanceWe propose that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis.
Highlights
Colorectal cancer (CRC) is a worldwide health problem with 655,000 deaths per year [1]
Conclusions/Significance: We propose that plasma miR-141 may represent a novel biomarker that complements Carcinoembryonic antigen (CEA) in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis
Carcinoembryonic antigen (CEA) has been used as a serum marker of CRC, its sensitivity has varied in different studies [5,6]
Summary
Colorectal cancer (CRC) is a worldwide health problem with 655,000 deaths per year [1]. In China, CRC remains the fifth most common cancer type and the fourth most common cause of cancer-related death [3]. A family of small regulatory RNAs, microRNAs, has emerged as possible plasma markers for human diseases including cancers due to their relative stability in the circulation [7]. Colorectal cancer (CRC) remains one of the major cancer types and cancer related death worldwide. Non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer
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