Circulating Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis

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.

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

“…15 In summary, this study sheds light on a group of miRNAs that are altered in TET and are emerging as putative non-invasive biomarkers for TET management. These findings might be useful to pave the way for additional and more detailed investigations to clarify the clinical usefulness of circulating miRNAs in TET.…”

Advances in epigenetic biomarker research in colorectal cancer

“…Many studies have been performed to quantify miRNAs in the blood for use as a biomarker (Table 4) [77][78][79][80][81][82][83][84][85][86][87][88] . miR-92a, located on chromosome 13q13, is a member of the miR-17-92 gene cluster.…”

“…In these studies, miR-221 and miR-21 were upregulated in the plasma of CRC patients compared to healthy controls [79,83] , while miR-601 and miR-760 were down-regulated [78] . Moreover, a study conducted in two independent CRC cohorts suggested that high levels of plasma miR-141 could predict poor survival, and thus miR-141 may serve as an independent prognostic factor for advanced CRC patients [81] .…”

miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4

“…Recent data have shown that miR-141 and miR-200c play important roles in tumorigenesis. For example, miR-141 increases in ovarian cancer (20) and colon cancer (21) and acts as an oncogene. Other researches show miR-141 is downregulated in renal cell carcinoma (22), breast cancer (23), and pancreatic cancer (24), and can inhibit cell growth in gastric cancer (25).…”