The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma

Zhi, Feng; Chen, Xi; Wang, Suinuan; Xia, Xiwei; Shi, Yimin; Guan, Wei; Shao, Naiyuan; Qu, Hongtao; Yang, Changchun; Zhang, Yi; Wang, Qiang; Wang, Rong; Zen, Ke; Zhang, Chen-Yu; Zhang, Junfeng; Yang, Yilin

doi:10.1016/j.ejca.2010.02.003

« Previous Next »European Journal of Cancer
Volume 46, Issue 9 , Pages 1640-1649, June 2010

The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma

Feng Zhi
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- These authors contributed equally to this work.
Xi Chen
- Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
- These authors contributed equally to this work.
Suinuan Wang
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Xiwei Xia
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Yimin Shi
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Wei Guan
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Naiyuan Shao
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Hongtao Qu
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Changchun Yang
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Yi Zhang
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Qiang Wang
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Rong Wang
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
Ke Zen
- Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
Chen-Yu Zhang
- Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
- Corresponding authors: Address: Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China. Tel./fax: +86 519 86180899 (Y. Yang).
Junfeng Zhang
- Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China
- Corresponding authors: Address: Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China. Tel./fax: +86 519 86180899 (Y. Yang).
Yilin Yang
- Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Department of Neurosurgery, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China
- Corresponding authors: Address: Research Institute of Modern Medicine, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu, China. Tel./fax: +86 519 86180899 (Y. Yang).

Received 21 August 2009; received in revised form 28 January 2010; accepted 5 February 2010. published online 11 March 2010.

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords: microRNA, Astrocytoma, Survival