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MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma.

ABSTRACT: Early detection is critical for the treatment of colon carcinoma. However, current biomarkers for its diagnosis and prognosis are insufficient and improvement is required. Aberrantly expressed microRNAs (miRNAs/miRs) in colon carcinoma have been identified to function as potential diagnostic and prognostic biomarkers. In the present study, 245 differentially expressed miRNAs between colon carcinoma and normal tissues were identified by a bioinformatics analysis of a dataset from The Cancer Genome Atlas. A six?miRNA (miR?149, miR?3189, miR?3677, miR?3917, miR?4999 and miR?6854) prognostic prediction system was established, which is able to independently and effectively predict the prognosis of colon carcinoma patients [P<0.001, area under the receiver operating characteristic curve (AUC)=0.763]. Furthermore, the six miRNAs were highly correlated with the tumor?nodes?metastasis (TNM) stage and were able to distinguish between different stages (high vs. low TNM stage, P<0.001). Of note, combination of the six?miRNA signature and TNM stage provides an improved prediction of the patient's prognosis (AUC=0.797). Functional enrichment analysis revealed the possible mechanistic involvement of these predictive miRNAs in cancer?associated biological processes and pathways. Taken together, the present study demonstrated the promising potential of the novel six?miRNA model as an independent factor for the prediction of the progression and prognosis of colon carcinoma.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6108873 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma.

Zhang Hui H Wang Zhuo Z Ma Rong R Wu Jianzhong J Feng Jifeng J

International journal of molecular medicine 20180725 4

Early detection is critical for the treatment of colon carcinoma. However, current biomarkers for its diagnosis and prognosis are insufficient and improvement is required. Aberrantly expressed microRNAs (miRNAs/miRs) in colon carcinoma have been identified to function as potential diagnostic and prognostic biomarkers. In the present study, 245 differentially expressed miRNAs between colon carcinoma and normal tissues were identified by a bioinformatics analysis of a dataset from The Cancer Genom ...[more]

PMID: 30066832

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Project description:PurposeExosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined.Experimental designMicroarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients.ResultsThe serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis.ConclusionExosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.

Project description:Background Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. To date, multiple panels of biomarkers have been described in ALS patients and murine models. Nevertheless, none of them has sufficient specificity and thus the molecular signature for ALS prognosis and progression remains to be fully elucidated. Circulating microRNAs (miRNAs) are highly stable molecules that are recently used as promising biomarkers for many types of human cancer and muscle disorders. Here we overcome this limitation through a longitudinal study, analyzing serum levels of circulating miRNAs in ALS patients during the progression of the pathology. Method We performed next-generation sequencing (NGS) analysis and absolute RT quantification of serum samples of 27 ALS patients and 11 healthy control; among them 13 ALS patients were studied every three months till the end of the disease. Results We demonstrated that miR-151a-3p, miR-206 and miR-199a-3p are significantly expressed at the mild, moderate and severe stages of ALS pathology, whereas the expression levels of miR-133a and miR-199a-5p remained low during the whole study and retain diagnostic significance in the moderate and severe stages (miR-133a) and in mild and terminal stages (miR-199a-5p) of the disease. Moreover, we analysed the miRNAs serum levels during the progression of the disease in each patient and we demonstrated that high levels of miR-206, miR-133a, miR-151a-5p, miR-151a-3p can predict a slower clinical decline of patient functionality suggesting that these miRNAs represent good potential prognostic markers for ALS disease. Conclusion This study is the first to perform a longitudinal absolute quantification of circulating miRNAs during ALS disease. We highlighted putative biomarkers for diagnosis, prognosis and disease stage identification of ALS patients providing cut-off threshold for most of the miRNAs analyzed. In addition, our results define a molecular signature of ALS phenotypes that could help to define appropriate enrollments of patients in clinical trials.

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MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma.

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MicroRNAs as biomarkers for the progression and prognosis of colon carcinoma.

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