Dataset Information

Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol.

ABSTRACT: To explore the role of miRNAs in colorectal cancers (CRC), we have deep sequenced 48 pairs of frozen CRC samples, of which 44 pairs produced high quality sequencing data. By using a combined approach of our bias reduction small RNA (smRNA) deep sequencing protocol and Illumina small RNA TruSeq method for sample bar coding, we have obtained data from samples of relatively large size with bias reduced digital profile results. This novel approach allowed us to validate many previously published results using various techniques to profile miRNAs in CRC tissues or cell lines and to characterize 'true' miRNA signatures highly expressed in colon/rectum (CR) or CRC tissues. According to our results, miR-21, a miRNA that is up-regulated in CRC, and miR-143, a miRNA that is down-regulated in CRC, are the two miRNAs that dominated the miRNA population in CR tissues, and probably are also the most important miRNAs in CRCs. These two miRNAs, together with the other eight miRNAs, miR-148a, -194, -192, 200b, -200c, -10b, -26a, and -145, with descending expressing levels, constituted the top 10 highly expressed miRNAs in CR/CRC. Using TaqMan miRNA qPCR, we detected the relative expression of some of the CRC miRNAs in 10 CRC cell lines, validated their dysregulation under cancer condition, and provided possible explanation for their dysregulation, which could be caused by APC, KRAS, or TP53 mutations. We believe these results will provide a new direction in future miRNA-related CRC development studies, and application of miRNAs in CRC diagnosis/prognosis, and therapy.

SUBMITTER: Sun G

PROVIDER: S-EPMC4826175 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol.

Sun Guihua G Cheng Ya-Wen YW Lai Lily L Huang Tsui-Chin TC Wang Jinhui J Wu Xiwei X Wang Yafan Y Huang Yasheng Y Wang Jinghan J Zhang Keqiang K Hu Shuya S Yang Ji-Rui JR Yen Yun Y

Oncotarget 20160101 4

To explore the role of miRNAs in colorectal cancers (CRC), we have deep sequenced 48 pairs of frozen CRC samples, of which 44 pairs produced high quality sequencing data. By using a combined approach of our bias reduction small RNA (smRNA) deep sequencing protocol and Illumina small RNA TruSeq method for sample bar coding, we have obtained data from samples of relatively large size with bias reduced digital profile results. This novel approach allowed us to validate many previously published res ...[more]

PMID: 26646696

Similar Datasets

Project description:Genomic technologies are reshaping the molecular landscape of colorectal cancer (CRC), revealing that oncogenic driver mutations (APC and TP53) coexist with still underappreciated genetic events. We hypothesized that mutational analysis of CRC-linked genes may provide novel information on the connection between genetically-deregulated pathways and clinical outcomes. We performed next-generation sequencing (NGS) analysis of 16 recurrently mutated genes in CRC exploiting tissue specimens from 98 advanced CRC patients. Multiple correspondence analysis (MCA) was used to identify gene sets characterizing negative and positive outliers (patients in the lowest and highest quartile of progression-free survival, PFS). Variables potentially affecting PFS and overall survival (OS) were tested in univariate and multivariate Cox proportional hazard models. Sensitivity analyses and resampling were used to assess the robustness of genomic predictors. MCA revealed that APC and TP53 mutations were close to the negative outlier group, whereas mutations in other WNT pathway genes were in proximity of the positive outliers. Reasoning that genetic alterations interact epistatically, producing greater or weaker consequences in combination than when individually considered, we tested whether patients whose tumors carried a genetic background characterized by APC and TP53 mutations without coexisting mutations in other WNT genes (AMER1, FBXW7, TCF7L2, CTNNB1, SOX9) had adverse survival outcomes. With this approach, we identified two oncodriver signatures (ODS1 and ODS2) associated with shorter PFS (ODS1 multivariate Cox for PFS: HR 2.16, 95%CI: 1.28-3.64, p?=?0.004; ODS2 multivariate Cox for PFS: HR 2.61, 95%CI: 1.49-4.58, p?=?0.001). Clinically-focused and molecularly-focused sensitivity analyses, resampling, and reclassification of mutations confirmed the stability of ODS1/2. Moreover, ODS1/2 negatively impacted OS. Collectively, our results point to co-occurring driver mutations as an adverse molecular factor in advanced CRC. This relationship depends on a broader genetic context highlighting the importance of genetic interactions.

Dataset Information

Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol.

Publications

Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets