Identification of biomarkers involved in the development of grade II meningiomas using the systems biology approach

Meningiomas are the most common primary brain tumors in adults. Most of them areidentified as benign (WHO grade I) and slow-growing lesions. Some Meningiomas are classified asatypical (WHO grade II), with increased mitotic activity, including four mitoses or more, spontaneousnecrosis, increased cellularity, and small cells with a high nuclear-to-cytoplasmic ratio(۱). MalignantMeningioma (WHO grade III) is associated with aggressive growth patterns reflecting their clinicaland histopathologic features of malignancy and can spread by metastatic dissemination. Here, weinvestigated the potential biomarkers of developing grade II meningiomas using systems biologyapproaches(۲).Microarray data, including ۱۴ meningioma samples, were obtained from the GEO database(GSE۷۷۲۵۹). The affy (۱.۸۰.۰) package in R(۴.۳.۲) was used to indicate gene expression profiling,evaluate data quality, and extract differentially expressed genes (DEG) between grade I and grade IIsamples. |log۲FC| ≥۰.۵۸, and p-value< ۰.۰۵ cutoff were set to identify the significant differentiallyexpressed genes. The weighted gene co-expression network analysis (WGCNA) package (۱.۷۲-۵) wasused to construct the co-expression network. Then, two modules were selected and visualized withCytoscape software (۳.۱۰.۱). Furthermore, Gene Ontology analyses were performed using theEnrichR database.Our results indicated ۲۹۴ genes were significantly differentially expressed in grade II compared to gradeI meningioma samples. Orange and lightcyan modules were selected among the identified modules.Three hub genes, including TCTEX۱D۱, KCNC۴, and TRUB۱, were significantly downregulated ingrade II vs grade I samples. These biomarkers have a role in ubiquitin-protein transferase inhibitoractivity and mRNA pseudouridine synthesis.The behavior and outcome of Grade II meningiomas are intermediate. Our analysis demonstrates somebiomarkers that may contribute to developing grade II meningiomas.

کلیدواژه ها:

Meningioma ، Differentially expressed genes ، Co-expression network ، WGCNA