Comparative Pathway Analysis of Glioblastoma and Astrocytoma Through Differential Gene Expression

Introduction Gliomas are primary tumors of neural system, that are caused by neuroglial cells, such as astrocytes and oligodendrocytes, that appear in nervous system. Astrocytoma (low grade glioma), and Glioblastoma multiform (GBM) (grade IV glioma) are among the various grades of gliomas according to WHO classification. There are various pathways related to gliomas such as MAP kinase cascade, p۵۳ apoptosis loss, alterations in cell cycle regulatory pathways and pathways related to VEGF. While GBM is the most malignant primary tumor of brain and also one of the rarest tumors overall, astrocytoma is the most common type of gliomas. EGFR, PTEN and TP۵۳ are among common genes that are altered in GBM but alterations in PI۳k/AKT/mTOR and MAPK signaling pathways are commonly seen in astrocytoma. Using bioinformatics methods to study cancer is both common and important. Soumya Alige Mahabala Rao and colleagues have conducted a research to understand differences between GBM and anaplastic astrocytoma. A research regarding progression of gliomas were also conducted by Adele Mazzoleni and colleagues. Identification of deferentially expressed genes (DEGs) can help us to comprehensively understand the genetic processes that happen in cancers and ways of interfering them by comparing two expression sets from two different samples. limma is one of the tools that can identify DEGs by using microarray data. We aim to investigate different pathways that are seen in GBM against astrocytoma by performing DEG analysis using limma package and performing pathway analysis. Methods Microarray researches in GEO were searched containing GBM and astrocytoma. GSE۱۶۰۱۱ were selected containing both cancers in adequate number. Box plot was illustrated to check the data for normality. Data were also checked to be in log of ۲. DEGs were identified using limma package. Contrasts were set between GBM and astrocytoma (GBM-A), top ۵۰ significantly down (GBM-A-down) and up (GBM-A-up) regulated genes were selected (p-value = ۰.۰۲, |logFC| > ۰.۵۸). Pathway analysis was performed using enrichr and reactome. Results Reactome pathways suggested that in GBM-A-up pathways were related to extracellular matrix (ECM) and cellular connections, such as collagen chain trimerization (p-value = ۵.۴۴E-۷), assembly of collagen fibrils (p-value = ۱.۱E-۵) and anchoring fibril formation (p-value = ۲.۱۹E-۵), were affected. Also, cell cycle pathways such as; G۲/M DNA replication checkpoint (p-value = ۱.۲۴E-۶), Cell Cycle, Mitotic (p-value = ۱.۱۴E-۶) and G۱/S Transition (p-value = ۱.۱۸E-۴). Both up and down regulated genes in GBM were involved in pathways related to possible progression of cancer according to Elsevier pathway collection such as Metaphase/Anaphase Phase Transition, TERT/WNT Activation in Cancer and also both were related to Proteins Involved in Glioblastoma. conclusion Our finding suggests some of the pathways that can be targeted in order to either prevent progression of astrocytoma to GBM or to control progression of GBM itself might be those related to cell to cell or cell to ECM connections such as collagen and anchoring fibrils.

کلیدواژه ها:

Glioblastoma Multiforme (GBM) ، Astrocytoma ، Glioma Pathways ، Cancer Bioinformatics ، Tumor Progression