Analysis of integrating PIK3CA and NF1 mutations into Glioblastoma multiforme prognostication and immunotherapy treatment strategy

Abstract

Abstract Objective The potential mechanisms of PIK3CA and NF1 expressions in GBM have been poorly elucidated. Risk-score analysis combined with clinicopathological characteristics to assess the prognostic value and immunotherapy efficacy of 6-genes signature. Methods We performed the whole exosome sequencing profiling on samples form patients with GBM. The association of PIK3CA and NF1 expression within the GBM have received cross-validations by MR methods and the risk-score analysis of 6-gene signature. The construction of 6 genes prognostic signature based on The Cancer Genome Atlas (TCGA) GBM cohort, the Gene Expression Omnibus (GEO), and IMvigor210 cohort. Results MR study demonstrated that PIK3CA and NF1 expressions were closely related with the risk of GBM patients by the IVW method. And then the construction of 6-gene signature was classified into high-risk and low-risk groups through the median risk-score of regression formula to predict prognosis of GBM patients. Kaplan-Meier survival showed the overall survival of distinct high- and low-risk groups. Receiver operating characteristic (ROC) curve analysis indicated the value of predictive performance of two different risk groups. In line with our WES reporters, our findings showed that the mutation of PIK3CA and NF1 was significantly associated with prognostic signature of GBM. Importantly, the individual altered gene took effect on response or resistance to ICB, such as PIK3CA. Consistent with our analysis about study individual mutations and their role in cancer immunotherapy, which might provide a novel insight on the mechanism of PIK3CA and NF1 mutation in the GBM. Conclusions Taken together, our MR analysis indicated the correlation between PIK3CA and NF1 expression and GBM disease, which provided a key basis for the precise prevention of the genetic mutation in the occurrence and development of GBM. The established PIK3CA and NF1 alteration-related prognostic signature was involved well in prognosis prediction as well as closely linked with immunotherapy responses. which also provided a novel and great potential in future clinical applications.