Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The rectal cancer microRNAome - a comprehensive comparative analysis of microRNA expression in rectal cancer and matched normal mucosa

ABSTRACT: Purpose: MicroRNAs play a prominent role in a variety of physiological and pathological biological processes, including cancer. For rectal cancers, only limited data are available on microRNA expression profiles, while the underlying genomic and transcriptomic aberrations have been firmly established. We therefore aimed to comprehensively map the microRNA expression patterns of this disease. Experimental design: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 72 patients (68 tumors and 70 normal mucosa) with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa microRNA expression profiles were subsequently established for all patients. The expression of selected microRNAs was validated using semi-quantitative real-time PCR. Results: Forty-nine microRNAs were significantly differentially expressed (log2-fold difference >0.5 and P<0.001) between rectal cancer and normal rectal mucosa. The predicted targets for the identified microRNAs were enriched for the following KEGG pathways: Wnt, TGF-beta, mTOR, insulin, MAPK, and ErbB signaling. Between rectal tumor and normal tissue, miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652*, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p were found to be differentially expressed. Of clinical impact, miR-135b expression correlated significantly with overall survival that could be validated in a larger multicenter patient set (n=94). Conclusion: The comprehensive analysis of the rectal cancer microRNAome uncovered novel microRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of rectal cancer. The identification and validation of miR-135b will help to identify novel molecular targets and pathways for therapeutic exploitation. Paired samples from rectal tumor and matched normal samples. Included are also 2 technical replicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Rolf SM-CM-8kilde

PROVIDER: E-GEOD-38389 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The rectal cancer microRNAome--microRNA expression in rectal cancer and matched normal mucosa.

Gaedcke Jochen J Grade Marian M Camps Jordi J Søkilde Rolf R Kaczkowski Bogumil B Schetter Aaron J AJ Difilippantonio Michael J MJ Harris Curtis C CC Ghadimi B Michael BM Møller Søren S Beissbarth Tim T Ried Thomas T Litman Thomas T

Clinical cancer research : an official journal of the American Association for Cancer Research 20120731 18

<h4>Purpose</h4>miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.<h4>Experimental design</h4>Tumor biopsies and corresponding matched mucosa samples were prospectively collecte ...[more]

PMID: 22850566

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Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.

Dataset Information

The rectal cancer microRNAome - a comprehensive comparative analysis of microRNA expression in rectal cancer and matched normal mucosa

Publications

The rectal cancer microRNAome--microRNA expression in rectal cancer and matched normal mucosa.

Similar Datasets

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