Prognosis and immunoinfiltration analysis of angiogene-related genes in grade 4 diffuse gliomas

Abstract

Although angiogenesis critically influences the progression of solid tumors, its contribution to highly malignant, grade 4 diffuse gliomas remains unclear. After analyzing 506 angiogenesis-related genes differentially expressed in grade 4 diffuse gliomas via LASSO and univariate and multivariate COX regression analyses, we constructed a nomogram based on COL22A1, IGFBP2, and MPO that accurately predicted patient survival. The nomogram's performance was validated in an external patient cohort, and a risk score based on the formula COL22A1*0.148+IGFBP2*0.234+MPO*0.145 was used to distinguish high-risk from low-risk patients. Based on differentially expressed genes among risk groups, functional enrichment and drug sensitivity analyses were conducted, and the association between COL22A1, IGFBP2, and MPO expression and infiltrating immune cells and immune checkpoint genes was investigated. We next focused on COL22A1, and verified its overexpression in both glioma cell lines and clinical samples. A pro-oncogenic role for COL22A1, evidenced by impaired proliferation, migration, and invasion capacities, was evidenced upon shRNA-mediated COL22A1 silencing in glioma U87 and LN18 cells. In summary, we present a novel nomogram based on the angiogenesis-related genes COL22A1, IGFBP2, and MPO that allows survival prediction in patients with grade 4 diffuse gliomas. Furthermore, our cellular assays support a pro-oncogenic role for COL22A1 in these tumors.

Identification of established and novel extracellular matrix components in glioblastoma as targets for angiogenesis and prognosis

“…Increased expression of COL6A1 and the vascular endothelial molecular marker cluster of differentiation ( CD31) induced glioma angiogenesis [61]. In another study, the authors developed a novel nomogram based on angiogenesis-related genes, including COL22A1 , which allowed survival prediction in patients with grade 4 diffuse gliomas [62]. In turn, COL5A1 has previously been associated with survival patterns in GBM patients (p < 0.0001).…”