Clinical and molecular analysis of cilia-associated gene signature for prognostic prediction in glioma.

Abstract

Glioma is a highly malignant and unfavorable cancer in the brain. Recent evidence highlights the vital role of cilia-related pathways as novel regulators of glioma development. However, the prognostic potential of ciliary pathways in glioma is still ambiguous. In this study, we aim to construct a gene signature using cilia-related genes to facilitate the prognostication of glioma. A multi-stage approach was employed to build the ciliary gene signature for prognostication of glioma. The strategy involved the implementation of univariate, LASSO, and stepwise multivariate Cox regression analyses based on TCGA cohort, followed by independent validation in CGGA and REMBRANDT cohort. The study further revealed molecular differences at the genomic, transcriptomic, and proteomic levels between distinct groups. A prognostic tool utilizing a 9-gene signature based on ciliary pathways was developed to assess the clinical outcomes of glioma patients. The risk scores generated by the signature demonstrated a negative correlation with patient survival rates. The validation of the signature in an independent cohort reinforced its prognostic capabilities. In-depth analysis uncovered distinctive molecular characteristics at the genomic, transcriptomic, and protein-interactive levels in the high- and low-risk groups. Furthermore, the gene signature was able to predict the sensitivity of glioma patients to conventional chemotherapeutic drugs. This study has established the utility of a ciliary gene signature as a reliable prognostic predictor of glioma patient survival. Findings not only enhance our comprehension of the intricate molecular mechanisms of cilia pathways in glioma, but also hold significant clinical implications in directing chemotherapeutic strategies.