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Identification of diagnostic serum protein profiles of glioblastoma patients.

Elstner A, Stockhammer F, Nguyen-Dobinsky TN, Nguyen QL, Pilgermann I, Gill A, Guhr A, Zhang T, von Eckardstein K, Picht T, Veelken J, Martuza RL, von Deimling A, Kurtz A - J. Neurooncol. (2010)

Bottom Line: Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects.No correlation was found with tumor size or age of the patient.These conceptual findings will be a basis for validation in a larger sample size.

View Article: PubMed Central - PubMed

Affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. anja.elstner@charite.de

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

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Related in: MedlinePlus

Tissue array based detection of protein expression in astrocytoma by immunohistochemistry. Magnification is ×400 for all sections. a Overview section of the tissue array used after detection of HSP70 by immunostaining. Each section represents an individual tumor or control tissue. Non-tumor control tissues are labeled with arrowheads. b, c FABP7 detection in b GBM and c control brain tissues. d, g HSP70 detection in d GBM and g control brain tissues. Arrows neurons, arrowheads glial cells. e, h IGFBP3 detection in e GBM and h control brain tissues. f, i TSP1 detection in f GBM and i control brain tissues
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Fig2: Tissue array based detection of protein expression in astrocytoma by immunohistochemistry. Magnification is ×400 for all sections. a Overview section of the tissue array used after detection of HSP70 by immunostaining. Each section represents an individual tumor or control tissue. Non-tumor control tissues are labeled with arrowheads. b, c FABP7 detection in b GBM and c control brain tissues. d, g HSP70 detection in d GBM and g control brain tissues. Arrows neurons, arrowheads glial cells. e, h IGFBP3 detection in e GBM and h control brain tissues. f, i TSP1 detection in f GBM and i control brain tissues

Mentions: Immunohistochemistry showed strong cytosolic expression of HSP70 and FABP7 in most GBM (Fig. 2). Some tumor cells showed nuclear presence of FABP7. Strong nuclear and perinuclear immunostaining of tumor cells was detected for TSP1, whereas IGFBP3 was expressed moderately in the cytoplasm. MDK expression was diffusely present in a minority of the tumors. BMP2 expression was negligible (not shown). In control brain sections IGFBP3 was not detectable. HSP70 was only detected in neurons and in a small number of astrocytes, TSP1 was strongly expressed and FABP7 expression was found in reactive astrocytes. Histoscore data for individual tumors and serum levels of matched samples did not correlate, even when tumor size was taken into account (not shown).Fig. 2


Identification of diagnostic serum protein profiles of glioblastoma patients.

Elstner A, Stockhammer F, Nguyen-Dobinsky TN, Nguyen QL, Pilgermann I, Gill A, Guhr A, Zhang T, von Eckardstein K, Picht T, Veelken J, Martuza RL, von Deimling A, Kurtz A - J. Neurooncol. (2010)

Tissue array based detection of protein expression in astrocytoma by immunohistochemistry. Magnification is ×400 for all sections. a Overview section of the tissue array used after detection of HSP70 by immunostaining. Each section represents an individual tumor or control tissue. Non-tumor control tissues are labeled with arrowheads. b, c FABP7 detection in b GBM and c control brain tissues. d, g HSP70 detection in d GBM and g control brain tissues. Arrows neurons, arrowheads glial cells. e, h IGFBP3 detection in e GBM and h control brain tissues. f, i TSP1 detection in f GBM and i control brain tissues
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3094565&req=5

Fig2: Tissue array based detection of protein expression in astrocytoma by immunohistochemistry. Magnification is ×400 for all sections. a Overview section of the tissue array used after detection of HSP70 by immunostaining. Each section represents an individual tumor or control tissue. Non-tumor control tissues are labeled with arrowheads. b, c FABP7 detection in b GBM and c control brain tissues. d, g HSP70 detection in d GBM and g control brain tissues. Arrows neurons, arrowheads glial cells. e, h IGFBP3 detection in e GBM and h control brain tissues. f, i TSP1 detection in f GBM and i control brain tissues
Mentions: Immunohistochemistry showed strong cytosolic expression of HSP70 and FABP7 in most GBM (Fig. 2). Some tumor cells showed nuclear presence of FABP7. Strong nuclear and perinuclear immunostaining of tumor cells was detected for TSP1, whereas IGFBP3 was expressed moderately in the cytoplasm. MDK expression was diffusely present in a minority of the tumors. BMP2 expression was negligible (not shown). In control brain sections IGFBP3 was not detectable. HSP70 was only detected in neurons and in a small number of astrocytes, TSP1 was strongly expressed and FABP7 expression was found in reactive astrocytes. Histoscore data for individual tumors and serum levels of matched samples did not correlate, even when tumor size was taken into account (not shown).Fig. 2

Bottom Line: Tumor expression and serum concentrations of 14 candidate proteins were analyzed for 23 GBM patients and nine healthy subjects.No correlation was found with tumor size or age of the patient.These conceptual findings will be a basis for validation in a larger sample size.

View Article: PubMed Central - PubMed

Affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. anja.elstner@charite.de

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

Show MeSH
Related in: MedlinePlus