This study is the first to systematically analyze and define a seven-gene signature (CTTNBP2, KIF18A, NAV1, SLAIN2, SRCIN1, TRIO, and TTBK2) and nomogram model closely associated with clinical factors and the tumor microenvironment as a reliable and independent prognostic biomarker to guide personalized choices of immunotherapy and chemotherapy for glioma patients. Here, TTBK2 is linked to central nervous system cancer.