Differential expression of serum miR-126,miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer

Objective:MicroRNAs(miRNAs) have potential as diagnostic biomarkers in cancer.Evaluation of the association between miRNA expression patterns and early detection of liver metastasis in colorectal cancer(CRC) has not been reported.Methods:We investigated the expression of metastasis-associated miRs-31,335,206,141,126,200b,200c,21,Let7a,Let7b and Let7c in localized,liver-metastatic and other organ-metastatic CRC(OM-CRC).Expressions of target miRNAs in serum were evaluated in 116 consecutive localized CRC(L-CRC),72 synchronous liver-metastatic CRC(SLM-CRC) and 36 other OM-CRC by quantitative real-time PCR.Results:Seven of 11 tested miRNAs could be detected from serum.Four miRNAs,miR-126,Let-7a,miR-141 and miR-21 were identified as metastasis-associated miRNAs.Compared with L-CRC,significant upregulated expression was observed for miR-141 and miR-21 in SLM-CRC and OM-CRC,down-regulated expression was observed for miR-126 in SLM-CRC and OM-CRC,and up-regulated expression of Let-7a in OM-CRC.The receiver operating characteristic(ROC) curve showed serum miR-126 had a cut-off [log 10 relative quantity(log 10 RQ)=–0.2005] with 77.78% sensitivity and 68.97% specificity with an area under curve(AUC) of 0.7564,miR-141 had a cut-off(log 10 RQ=–0.2285) with 86.11% sensitivity and 76.11% specificity with an AUC of 0.8279,and miR-21 had a cut-off(log 10 RQ=–0.1310) with 73.61% sensitivity and 66.38% specificity with an AUC of 0.7479.Conclusions:We identified liver metastasis-associated miRNAs,suggesting serum miR-126,miR-141 and miR-21 may be novel biomarkers for clinical diagnosis of early stage liver-metastatic CRC.