[Show abstract][Hide abstract] ABSTRACT: The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan-Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two-phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14-miRNA profile differed between tumor and NAT samples. Downregulation of miR-29c-3p and miR-219-5p were found to be associated with advanced clinical stages of meningioma. Kaplan-Meier analysis showed that high expression of miR-190a and low expression of miR-29c-3p and miR-219-5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR-190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes.
International Journal of Cancer 06/2012; · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases including cancers. In the present study, the miRNA expression profile was examined in astrocytoma, a malignant and prevalent intracranial tumour in adults.
We screened the expression profile of 200 miRNAs in a training sample set consisting of 84 astrocytoma samples and 20 normal adjacent tissue (NAT) samples using the method of stem-loop quantitative RT-PCR. The significantly altered miRNAs were validated in another independent sample set consisting of 40 astrocytoma samples and 40 NAT samples. The correlation of the miRNA levels with survival in astrocytoma samples was estimated by performing Kaplan-Meier survival analysis and univariate/multivariate Cox proportional hazard regression analysis.
After a two-phase selection and validation process, seven miRNAs were found to have a significantly different expression profile in astrocytoma samples upon comparison to the NAT samples. Unsupervised clustering analysis further revealed the great potential of the 7-miRNA profile to differentiate between tumours and normal brain tissues. The down-regulation of hsa-miR-137 in astrocytomas was shown to be associated with advanced clinical stages of this disease. Using Kaplan-Meier survival analysis we showed that low expression of hsa-miR-181b or hsa-miR-106a, or high expression of hsa-miR-21 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors.
Our results suggest a great potential for the use of miRNA profiling as a powerful diagnostic and prognostic marker in defining the signature of astrocytomas and in predicting the post-surgical outcome.
European journal of cancer (Oxford, England: 1990) 03/2010; 46(9):1640-9. · 4.12 Impact Factor