Rao, Soumya Alige Mahabala and Srinivasan, Sujaya and Patric, Irene Rosita Pia and Hegde, Alangar Sathyaranjandas and Chandramouli, Bangalore Ashwathnarayanara and Arimappamagan, Arivazhagan and Santosh, Vani and Kondaiah, Paturu and Rao, Manchanahalli Sathyanarayana R and Somasundaram, Kumaravel (2014) A 16-Gene Signature Distinguishes Anaplastic Astrocytoma from Glioblastoma. In: PLOS ONE, 9 (1).
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Abstract
Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM) and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT) pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLOS ONE |
| Publisher: | PUBLIC LIBRARY SCIENCE |
| Additional Information: | Copyright for this article belongs to the authors. |
| Department/Centre: | Division of Biological Sciences > Centre for Neuroscience Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Molecular Reproduction, Development & Genetics |
| Date Deposited: | 06 Mar 2014 06:59 |
| Last Modified: | 06 Mar 2014 06:59 |
| URI: | http://eprints.iisc.ac.in/id/eprint/48497 |
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