Stats outsmarting brain tumours

CSIRO and the Kolling Institute of Medical Research at Sydney's Royal North Shore Hospital have discovered two new biological markers that can identify different types of aggressive brain tumours.

The discovery was announced this month in the Journal of Neuropathology and Experimental Neurology. It is hoped that it will assist neuropathologists to more accurately diagnose brain tumours and better predict patient survival.

The work used statistical techniques developed by CSIRO Mathematical & Information Sciences. See When p is greater than n

"CSIRO's statistical techniques have advanced the Institute's brain tumour research by up to five years," the Kolling Institute's Dr Kerrie McDonald said.

Using samples of brain tumours and normal brain tissue obtained from the Australasian Brain Tumour Bank at Royal North Shore Hospital, McDonald's team measured the expression of thousands of different genes.

CSIRO statistician Maree O'Sullivan said researchers typically observe hundreds of different gene expression changes in tumour samples.

"Our statistical techniques are able to sort through the data and pinpoint very small sets of genes that reliably differentiate between tumour types," O'Sullivan said.

The Kolling team identified a signature gene expression pattern of 18 genes that is unique to aggressive brain tumours and absent in normal tissue.

"Two of the genes have been validated at the protein level and we have found that expression levels are associated with survival outcome," McDonald said.

Microarray expression analysis and immunohistochemistry were used to identify the biomarkers associated with the more aggressive gliomas.

The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor.

In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than three years was observed.

The researchers said the use of these markers confirmed a non-uniform distribution of survival in those with grade III and IV tumours. "Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information," they wrote.

As well as vastly speeding up the research, the findings could lead to a fast and inexpensive gene-based diagnostic test.

CSIRO is also using its proprietary statistical techniques to develop diagnostic and prognostic tools for other types of cancer, including predicting survival time for breast cancer patients and diagnosing subtypes of paediatric acute lymphoblastic leukaemia to enable individualised treatment.

For more information, see J Neuropathol Exp Neurol Vol. 66, No. 5 May 2007: "IQGAP1 and IGFBP2: Valuable Biomarkers for Determining Prognosis in Glioma Patients"