Investigating the rapid diagnosis of gliomas from serum samples using infrared spectroscopy and cytokine and angiogenesis factors

Abstract

The ability to diagnose brain cancer rapidly from serum samples is of great interest; such a diagnosis would allow for rapid testing and time to results providing a responsive diagnostic environment, ability to monitor treatment efficacy, early detection of recurrent tumours and screening techniques. Current methods rely upon subjective, time-consuming tests such as histological grading and are particularly invasive with the diagnostic test requiring hospitalisation of 2-3 days. A rapid diagnostic method based upon serum samples would allow for a relatively non-invasive test and open up the possibility of screening for brain cancer. We report for the first time the use of a Bioplex immunoassay to provide cytokine and angiogenesis factor levels that differ between serum from glioma and non-cancer patients specifically angiopoietin, follistatin, HGF, IL-8, leptin, PDGF-BB and PECAM-1 providing sensitivities and specificities as high as 88 % and 81 %, respectively. We also report, for the first time, the use of serum ATR-FTIR combined with a RBF SVM for the diagnosis of gliomas from non-cancer patients with sensitivities and specificities as high as 87.5 % and 100 %, respectively. We describe the combination of these techniques in an orthogonal diagnostic regime, providing strength to the diagnosis through data combinations, in a rapid diagnostic test within 5 h from serum collection (10 min for ATR-FTIR and 4 h for the Bioplex Immunoassay). This regime has the ability to revolutionise the clinical environment by providing objective measures for diagnosis allowing for increased efficiency with corresponding decreases in mortality, morbidity and economic impact upon the health services.

Assessing the challenges of Fourier transform infrared spectroscopic analysis of blood serum

“…The application of ATR to serum and plasma sample analysis is currently highly favoured in the community [7,8,29,30]. In our experience we found the technique to be fairly practical, especially for the larger molecular weight fraction, producing high reproducibility.…”

“…The focus of our blood research is prostate cancer (CaP), therefore we demonstrate the use of different methods on a sample of male human blood serum as a model. In current investigations of methodology, sub-fractioning of serum samples is yet another configuration option to consider [5,7]. Inevitably this approach adds to the sample preparation, however, at this early stage of analysis, separating the whole serum into sub-fractions also reduces the spectral complexity ( Figure 1).…”

“…Over the years, there have been frequent reports of both transmission and attenuated total reflectance (ATR) measurements of blood-derived samples for diagnostic applications such as bovine spongiform encephalopathy (BSE) [4], cardiology [5], bladder cancer [6], brain cancer [7] and ovarian cancer [8]. On first inspection, the application of infrared spectroscopy for the analysis of blood serum may seem straight forward to the uninitiated.…”

Vibrational spectroscopy of biofluids for disease screening or diagnosis: translation from the laboratory to a clinical setting

“…Bio-Plex Pro TM immunoassays provide cytokine and angiogenesis factor levels that differ between serum from glioma vs. non-cancer patients; specifically angiopoietin, follistatin, hepatocyte growth factor (HGF), interleukin 8 (IL-8), leptin, platelet-derived growth factor (PDGF)-BB [composed of two B chains] and platelet endothelial cell adhesion molecule-1 (PECAM-1); on its own, this test gave sensitivities and specificities as high as 88% and 81%, respectively. With ATR-FTIR spectroscopy, sensitivities and specificities of 87.5% and 100% were achieved, respectively; this suggests that combination of these techniques in an orthogonal diagnostic regime could provide enhanced diagnostic capability [48].…”

“…With 30 patients in each group that is in itself a bias, clearly larger datasets with different grades and sub-types of ovarian cancer are needed to validate this study but these findings suggest what this area can offer in the screening and diagnosis of this disease. ATR-FTIR spectroscopy has been used to demonstrate a high level of diagnostic accuracy in the detection and classification of gliomas, malignant brain tumours that are responsible for 50% of intracranial lesions [48,49]. Current diagnostic options for these types of tumours include CT and magnetic resonance imaging (MRI) scans but ultimately these rely on an inpatient diagnostic brain biopsy, a highly invasive procedure.…”