en Brain Tumors Research <strong>Background and Aim:</strong> Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor with poor prognosis, largely driven by glioma stem-like cells (GSCs). Novel biomarkers that both characterize GSCs and predict patient survival are urgently needed. This study aims to identify GSCrelated genes with prognostic value in GBM through integrated bioinformatics analyses.<br> <strong>Methods and Materials/Patients:</strong> Microarray data (GSE23806) comparing glioma cell lines and GSCs were downloaded via GEOquery in R and normalized. Differentially expressed genes (DEGs) were identified using the limma package (log₂ fold change &ge;1, adjusted P<0.01). DEGs were crossreferenced with TCGA GBM tumor data via GEPIA2 to find common dysregulated genes. Kaplan&ndash; Meier survival analyses were performed using GEPIA2 to identify genes associated with survival. Protein&ndash;protein interaction (PPI) networks were built using GeneMANIA in cytoscape. Functional enrichment analyses (GO and KEGG) were conducted using clusterProfiler, with q<0.01.<br> <strong>Results:</strong> A total of 1212 DEGs were i SMAD13 dentified in GSCs vs glioma cell lines and 5224 DEGs in GBM tumors vs normal tissues; 355 genes were commonly differentially expressed. Survival analysis revealed six genes (APLP1, CA14, PTPRN2, POR, ARMC10, and SMAD13) significantly associated with overall survival. Among these, CA14 and SMAD13 appeared protective (Hazzard ratio [R]~0.53&ndash;0.56), while APLP1, PTPRN2, POR, and ARMC10 were associated with risk (HR 1.6&ndash; 1.7). A PPI network with 26 nodes and 256 edges underscored extensive functional interactions. Enrichment analyses highlighted dysregulation in pathways including hypoxia response, metabolic processes, TGF&beta; signaling, and stem-like phenotypes.<br> <strong>Conclusion:</strong> Our integrated bioinformatics framework identified six novel GSC-related genes with prognostic significance in GBM, representing diverse biological roles that range from tumor suppression to oncogenic signaling. These genes hold promise as diagnostic or therapeutic targets, but require experimental validation, including gene expression assays and functional studies to substantiate their roles in GBM pathogenesis and therapy resistance. Glioblastoma multiforme, bioinformatics, cancer stem cells, glioma cancer cells, signaling pathway 0 0 http://irjns.org/browse.php?a_code=A-10-467-1&slc_lang=en&sid=1 Haniye Abbasi 100319475328460012555 100319475328460012555 No Saman Morovat 100319475328460012556 100319475328460012556 No Shahrokh Yousefzadeh-Chabok 100319475328460012557 100319475328460012557 No Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran. Seyedeh Elham Norollahi 100319475328460012558 100319475328460012558 No Fatemeh Nejatifar 100319475328460012559 100319475328460012559 No Kourosh Delpasand 100319475328460012560 100319475328460012560 No Department of Medical Ethics, Guilan University of Medical Sciences, Rasht, Iran. Kosar Babaei Babaei.kosar@yahoo.com 100319475328460012561 100319475328460012561 No Afshin Dalili 100319475328460012563 0009-0003-0030-8523 No Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran Ali Akbar Samadani a.a.hormoz@gmail.com 100319475328460012562 100319475328460012562 Yes Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran