A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.
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.
Department of Microbiology and Cell Biology, Development and Genetics, Indian Institute of Science, Bangalore, India.
Soumya Alige Mahabala
SA
Rao
Department of Microbiology and Cell Biology, Development and Genetics, Indian Institute of Science, Bangalore, India.
Sujaya
S
Srinivasan
Department of Microbiology and Cell Biology, Development and Genetics, Indian Institute of Science, Bangalore, India.
Irene Rosita Pia
IR
Patric
Sri Sathya Sai Institute of Higher Medical Sciences, Bangalore, India.
Alangar Sathyaranjandas
AS
Hegde
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Bangalore Ashwathnarayanara
BA
Chandramouli
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Arivazhagan
A
Arimappamagan
Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Vani
V
Santosh
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Paturu
P
Kondaiah
Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Manchanahalli R Sathyanarayana
MR
Rao
Department of Microbiology and Cell Biology, Development and Genetics, Indian Institute of Science, Bangalore, India.
Kumaravel
K
Somasundaram
D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D015203:Reproducibility of Results; D059467:Transcriptome; D055815:Young Adult
D014408:Biomarkers, Tumor