Abstract
The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients. Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis. Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs. Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis.
Highlights
An immediate need in oncology is biomarkers, which can be identified through simple noninvasive or less invasive methods with the potential to identify cancer risk, promote early diagnosis, grade accurately, and monitor treatment response [1, 2]
Astrocytomas are further divided into pilocytic astrocytoma, diffuse astrocytoma (DA; grade II), anaplastic astrocytoma (AA; grade III), and glioblastoma (GBM; grade IV), whereas oligodendrogliomas are classified as diffuse oligodendroglioma (DO; grade II) and anaplastic oligodendroglioma (AO; grade III)
Tumor samples Tumor samples were collected from patients who were operated at National Institute of Mental Health and Neurosciences (NIMHANS) and Sri Satya Sai Institute of Higher Medical Sciences (SSIHMS), Bangalore, India
Summary
An immediate need in oncology is biomarkers, which can be identified through simple noninvasive or less invasive methods with the potential to identify cancer risk, promote early diagnosis, grade accurately, and monitor treatment response [1, 2]. Secreted proteins can be used as circulating tumor markers for diagnosis and monitoring patient response to treatment. Gliomas are the most common primary central nervous system tumors of the brain. They include astrocytomas, oligodendrogliomas, and oligoastrocytomas based on type of cells they originate from, with the latter having components of both cell types [3]. The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
