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） ha...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,miR141 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 [log10 relative quantity （log10RQ）=--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 （1og10RQ=-0.2285） with 86.11％ sensitivity and 76.11％ specificity with an AUC of 0.8279,and miR-21 had a cut-off （log10RQ=-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.展开更多
Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes i...Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting(LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.展开更多
文摘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,miR141 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 [log10 relative quantity （log10RQ）=--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 （1og10RQ=-0.2285） with 86.11％ sensitivity and 76.11％ specificity with an AUC of 0.8279,and miR-21 had a cut-off （log10RQ=-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.
基金supported by grants from the National Basic Research Program(973Program No.2012CB934002,2010CB912802)National Key Scientific instrument Special Programme of China(Grant No.2011YQ03013405)National Science Foundation of China(Grant No.81121004,81071953)
文摘Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting(LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.
