The Overexpression of <scp>RTN4</scp> Significantly Associated With an Unfavourable Prognosis in Patients With Lower‐Grade Gliomas

Gliomas, the most prevalent primary malignancy of the central nervous system, is characterised by its high mortality rates and unfavourable prognosis. Despite extensive research, the underlying mechanisms of glioma pathogenesis remain elusive. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases provided the lower-grade gliomas (LGG) transcriptome and related clinical data, which were downloaded separately. It was determined what the clinical data differences were between the two groups based on the median reticulon-4 (RTN4) expression group. The R language's survminer tool was utilised to examine the variations in survival between the RTN4 high and low-expression groups. The GeneMANIA database was searched for genes that might interact with RTN4, and these genes were then used to create extensive coexpression networks. Cox regression analysis, both univariate and multivariate, was used to filter out the independent prognostic factors influencing tumour growth. Based on independent prognostic parameters, a nomogram was created to predict prognosis. The model was assessed both internally and externally using receiver operating characteristic curve (ROC) and correcting curves. The R cibersort package was utilised to assess the level of immune infiltration abundance. We further validated our findings with clinical tissues using immunohistochemistry approaches. Statistical significance was determined using the Wilcoxon signed-rank test, with a p value of < 0.05 considered significant. RTN4 expression in the tumour group was higher than in the normal group (p < 0.001), and a high-expression level was linked to a poor prognosis (p = 0.028). Patients with elevated RTN4 expression exhibited significant differences from normal brain tissue samples when stratified analysis of LGG patients by sex or radiation treatment was performed (p < 0.001). The immune cell infiltration data demonstrated that the two groups' expressions of various immune cells differed, with pDC cells showing the greatest correlation (-0.421). Univariate and multivariate Cox regression study showed that RTN4, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion and nia age could be employed as independent prognostic factors for LGG, and the correction curve of the model fit well. Ultimately, clinical samples' immunohistochemistry revealed that RTN4 was markedly overexpressed in low-grade gliomas. High RTN4 expression was strongly associated with a poor prognosis in LGG patients. RTN4 may serve as a prognostic biomarker for patients with LGG and represents a potential therapeutic target for immunotherapy in this patient population.