Identification of diagnostic serum protein profiles of glioblastoma patients

Abstract

Objective Diagnosis of a glioblastoma (GBM) is triggered by the onset of symptoms and based on cerebral imaging and histological examination. Serum based biomarkers may support detection of GBM. Here, we explored serum protein concentrations in GBM patients and used data mining to explore profiles of biomarkers and whether these associate with clinical status of the GBM patients. Methods Gene and protein expression data for astrocytoma and GBM were used to identify secreted proteins differentially expressed in tumors versus normal brain tissues. The tumor expression and serum concentrations of 14 candidate proteins were analyzed in 23 GBM patients and 9 healthy subjects. Data mining methods involving all 14 proteins were applied as an initial evaluation step to find clinically informative profiles. Results Data mining identified a serum protein profile formed by BMP2, HSP70 and CXCL10 that allowed correct assignment into the GBM group with a specificity and sensitivity of 89% and 96%, respectively (p<0.0001, Fischer's exact test). Survival after tumor resection for more than 15 month was associated with a profile formed by TSP1, HSP70 and IGFBP3, allowing correct assignments in all cases (p<0.0001, Fischer's exact test). No correlation was found with tumor size and age of the patient. Conclusion The study shows that robust serum profiles for GBM may be identified by data mining based on a relatively small study cohort. Profiles of more than one biomarker allow a more specific assignment to the GBM and survival group than single proteins, confirming earlier attempts to correlate single markers with cancer. These findings will be a basis for validation in a larger sample size.

MicroRNA-21 Promotes Glioblastoma Tumorigenesis by Down-regulating Insulin-like Growth Factor-binding Protein-3 (IGFBP3)

“…For example, IGFBP3 was found to be among a group of serum markers in GBM associated with prolonged survival (15 months) after tumor resection in a cohort of 23 patients (36). IGFBP3 reportedly can have antiproliferative or growth promoting actions on tumor cells (34).…”

The investigation of changes in proteins expression (Apolipoprotein A1 and albumin) in malignant astrocytoma brain tumor

“…[19 -22] The aims, experimental design, methodology and analysis, classification of control brain and size of these studies has been different and there appear inconsistency in some findings. [23] The vascular microenvironment of glioma play a major role in determining the pathophysiological character is tics of the tumor. [24] Growing tumors reach a point at which the existing blood supply can no longer support the needs of the tumor leading to areas of hypoxia.…”

Human expression patterns: qualitative and quantitative analysis of thrombospondin‐1 under physiological and pathological conditions

“…In pancreatic cancer, serum TSP‐1 is down‐regulated in patients with cancer . In glioblastoma, no significant difference is observed in serum TSP‐1 levels in patients compared to healthy subjects, but higher pre‐surgery serum TSP‐1 is prognostic of longer survival in patients after tumour resection . Overall, these data suggest that the cancer‐driven regulation of TSP‐1 expression in humans may be highly dependent on the specific cancer types and clinical stage and deserves further investigation.…”

“…The potential of circulating and tissue TSP‐1 protein as diagnostic or prognostic markers for cancers, given its anti‐angiogenic and pro‐apoptotic properties, has been studied extensively. Table summarizes the quantitatively measured TSP‐1 protein levels in the plasma, serum, platelet and tissue of individuals with various cancer conditions . Most measured values of plasma TSP‐1 protein levels are in the range of a few hundred to a few thousand ng/mL, indicating that physiological TSP‐1 concentrations are relatively low in the circulation .…”