COL4A1 as a novel oncogene associated with the clinical characteristics of malignancy predicts poor prognosis in glioma

Abstract

Studies have indicated that collagen α-1 (IV) chain (COL4A1) has an indispensable regulatory role in the complex pathological mechanisms of numerous types of malignant tumor. However, its role in the development of glioma has remained elusive. Therefore, the present study sought to determine the association between the expression levels of COL4A1 and the clinical characteristics of gliomas by analyzing large samples. First, analysis of thousands of glioma tissue samples collected from the Gene expression profiling interactive analysis, Gene Expression Omnibus database, the Ivy glioblastoma atlas, The Human Protein Atlas, Chinese Glioma Genome Atlas and The Cancer Genome Atlas. In addition, glioma tissues and normal brain tissues from patients with glioma and epilepsy undergoing surgical resection were collected. These samples, which were subjected to a variety of different detection techniques (including sequencing data, chip data, reverse transcription-quantitative PCR, cell lines and tissue samples, in situ hybridization and immunology) revealed that COL4A1 expression was not only increased at the mRNA level but also at the protein level as compared with that in normal brain tissue. Furthermore, Kaplan-Meier analysis revealed that COL4A1 expression was associated with reduced overall survival of patients, particularly those with World Health Organization grade III glioma. Receiver operating characteristic analysis suggested that COL4A1 had a moderate diagnostic value for glioma. In addition, the Mann-Whitney U-test or Kruskal-Wallis test indicated that the expression levels of COL4A1 were positively associated with the histological type and historical grade of the tumor, patient age, 'Primary, Recurrent, Secondary' type and the chemotherapy status, and negatively associated with isocitrate dehydrogenase mutation and 1p19q co-deletion (P<0.001). Gene-set enrichment analysis indicated that overexpression of COL4A1 promoted cancer-associated pathways, such as the JAK/STAT signaling pathway and cell cycle regulation. Finally, an MTT assay, immunohistochemical analysis of the cell cycle regulator KI67 and a wound-healing assay further confirmed that knockdown of COL4A1 inhibited the proliferation and migration ability of glioma cells. In conclusion, COL4A1, as a novel oncogene, is a marker for poor prognosis in patients with glioma. The present study expanded the understanding of the pathogenesis of glioma and identified COL4A1 as a potential target for the diagnosis and treatment of gliomas.

MRI Elastography Identifies Regions of Extracellular Matrix Reorganization Associated with Shorter Survival in Glioblastoma Patients

“…NRP1 and DAB2 have been linked to glioma progression 35,36 , PECAM1 correlates with GBM aggressiveness 37 , CD163 is positively associated with the glioma malignancy grade 38 , and Flt1 promotes invasion and migration of glioblastoma cells 39 . CR1, PLAGL1, COL4A1, and COL5A2 have all been shown to correlate with shorter survival [40][41][42][43] .…”

The complex interactions between the cellular and non-cellular components of the brain tumor microenvironmental landscape and their therapeutic implications

“…These collagens are essential components of the basal lamina of the basement membrane and are characterized by the presence of NC (No-collagen) domain at the N and C terminal ends that enable the formation of collagen networks ( 5 , 179 ). Collagen IV is localized at the base membrane surrounding the blood vessels and it is upregulated in gliomas ( 180 , 181 ).The third subtype of collagens are the fibril-associated collagens (FACIT), including collagen XVI. These molecules present interrupted triple helices and, although they do not form fibrils by themselves, bind to other ECM proteins such as proteoglycans and small leucin rich proteoglycans (SLRPs) then are further stabilized by the lysyl oxidase enzymes (LOXs) ( 5 , 182 , 183 ).…”

Comprehensive analysis of the collagen family members as prognostic markers in clear cell renal cell carcinoma

“…COL1A1 expression level can be used to predict the prognosis and immunotherapy effect of gastric cancer patients (8). Besides, COL4A1 is an active oncogene in glioma and is associated with tumor stage and prognosis (9). COL6A3 polymorphisms were associated with lung cancer risk (10).…”