Dataset Information

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

ABSTRACT: The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be prognostic [p = 1.28E-07, HR 8.4 (95 % CI: 3.81-18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.

SUBMITTER: Bobowicz M

PROVIDER: S-EPMC5110606 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

Bobowicz Maciej M Skrzypski Marcin M Czapiewski Piotr P Marczyk Michał M Maciejewska Agnieszka A Jankowski Michał M Szulgo-Paczkowska Anna A Zegarski Wojciech W Pawłowski Ryszard R Polańska Joanna J Biernat Wojciech W Jaśkiewicz Janusz J Jassem Jacek J

Clinical & experimental metastasis 20160802 8

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of pat ...[more]

PMID: 27485175

Similar Datasets

Project description:BACKGROUND:The aim was to identify a novel prognostic miRNA signature for colon cancer (CC) in silico. METHODS:Data on the expression of miRNAs and relevant clinical information for 407 patients were obtained from The Cancer Genome Atlas (TCGA), and the samples were randomly split into a validation set (n = 203) and training set (n = 204). The differential expression of miRNAs between normal tissues and patients with CC was analyzed. We detected a miRNA expression signature in the training dataset by using a Cox proportional hazard regression model. Then, we verified the signature in the validation set. Association of the miRNA signature with overall survival was assessed in the validation cohort and combined cohort by log-rank test and based on Kaplan-Meier curves. The receiver operating characteristic and disease-free survival analyses were performed to evaluate the miRNA signature of CC in the combined cohort. Multivariate and univariate Cox analyses related to survival for the miRNA signature were performed, and a nomogram was built as a prognostic model for CC. To explore the function of target genes of the miRNA signature, Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used. RESULTS:Between the matched normal tissues and colon cancer tissues, 267 differentially expressed miRNAs were detected, and a single-factor CoxPH model showed that 13 miRNAs were related to overall survival in the training cohort. Then, a five-miRNA signature was identified using a CoxPH regression model with multiple factors. The five-miRNA signature had significant prognostic value in the training cohort and was validated in the validation cohort and combined cohort. A total of 193 target genes of the miRNA signature were identified. According to the results of functional analysis of the target genes, the signaling pathways MAPK, AMPK and PI3K-Akt, focal adhesion, and microRNAs in cancer were remarkably enriched. CONCLUSION:A five-miRNA signature had increased prognostic value for CC, which may provide important biological insights for the discovery and development of molecular predictors to improve the prognosis of patients with CC.

Dataset Information

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

Publications

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets