On the relevance of glycolysis process on brain gliomas.

The proposed analysis considers aspects of both statistical and biological validation of the glycolysis effect on brain gliomas, at both genomic and metabolic level. In particular, two independent datasets are analyzed in parallel, one engaging genomic (Microarray Expression) data and the other metabolomic (Magnetic Resonance Spectroscopy Imaging) data. The aim of this study is twofold. First to show that, apart from the already studied genes (markers), other genes such as those involved in the human cell glycolysis significantly contribute in gliomas discrimination. Second, to demonstrate how the glycolysis process can open new ways towards the design of patient-specific therapeutic protocols. The results of our analysis demonstrate that the combination of genes participating in the glycolytic process (ALDOA, ALDOC, ENO2, GAPDH, HK2, LDHA, LDHB, MDH1, PDHB, PFKM, PGI, PGK1, PGM1 and PKLR) with the already known tumor suppressors (PTEN, Rb, TP53), oncogenes (CDK4, EGFR, PDGF) and HIF-1, enhance the discrimination of low versus high-grade gliomas providing high prediction ability in a cross-validated framework. Following these results and supported by the biological effect of glycolytic genes on cancer cells, we address the study of glycolysis for the development of new treatment protocols.

Strengths and weaknesses of 1.5T and 3T MRS data in brain glioma classification.

Although magnetic resonance spectroscopy (MRS) methods of 1.5Tesla (T) and 3T have been widely applied during the last decade for noninvasive diagnostic purposes, only a few studies have been reported on the value of the information extracted in brain cancer discrimination. The purpose of this study is threefold. First, to show that the diagnostic value of the information extracted from two different MRS scanners of 1.5T and 3T is significantly influenced in terms of brain gliomas discrimination. Second, to statistically evaluate the discriminative potential of publicly known metabolic ratio markers, obtained from these two types of scanners in classifying low-, intermediate-, and high-grade gliomas. Finally, to examine the diagnostic value of new metabolic ratios in the discrimination of complex glioma cases where the diagnosis is both challenging and critical. Our analysis has shown that although the information extracted from 3T MRS scanner is expected to provide better brain gliomas discrimination; some factors like the features selected, the pulse-sequence parameters, and the spectroscopic data acquisition methods can influence the discrimination efficiency. Finally, it is shown that apart from the bibliographical known, new metabolic ratio features such as N-acetyl aspartate/ S, Choline/ S, Creatine/ S , and myo-Inositol/ S play significant role in gliomas grade discrimination.

Revealing the metabolic profile of brain tumors for diagnosis purposes.

The metabolic behavior of complex brain tumors, like Gliomas and Meningiomas, with respect to their type and grade was investigated in this paper. Towards this direction the smallest set of the most representative metabolic markers for each brain tumor type was identified, using ratios of peak areas of well established metabolites, from (1)H-MRSI (Proton Magnetic Resonance Spectroscopy Imaging) data of 24 patients and 4 healthy volunteers. A feature selection method that embeds Fisher's filter criterion into a wrapper selection scheme was applied; Support Vector Machine (SVM) and Least Squares-SVM (LS-SVM) classifiers were used to evaluate the ratio markers classification significance. The area under the Receiver Operating Characteristic curve (AUROC) was adopted to evaluate the classification significance. It is found that the NAA/CHO, CHO/S, MI/S ratios can be used to discriminate Gliomas and Meningiomas from Healthy tissue with AUROC greater than 0.98. Ratios CHO/S, CRE/S, MI/S, LAC/CRE, ALA/CRE, ALA/S and LIPS/CRE can identify type and grade differences in Gliomas giving AUROC greater than 0.98 apart from the scheme of Gliomas grade II vs grade III where 0.84 was recorded due to high heterogeneity. Finally NAA/CRE, NAA/S, CHO/S, MI/S and ALA/S manage to discriminate Gliomas from Meningiomas providing AUROC exceeding 0.90.