Lin Xie, Anmin Liu, Qinbiao Chen, Min Luo, Linlin Lu, Wenjing Lin, Cheng Zhong
Objective: The potential mechanisms of NF1, Phosphatidylinositol-4,5-bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) and Neurofibromatosis 1 (NF1) expressions in Glioblastoma Multiforme (GBM) have been poorly elucidated. Risk-score analysis combined with clinic pathological 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 Mendelian Randomization (MR) methods and the risk-score analysis of 6-gene signature.
Results: MR study demonstrated that PIK3CA and NF1 expressions were closely related with the risk of GBM patients by the Inverse Variance Weighting (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 Whole Exome Sequencing reporters (WES), our findings showed that the mutation of PIK3CA and NF1 was significantly associated with prognostic signature of GBM.
Conclusion: 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.