Identification and validation of chromatin regulator-related signatures as a novel prognostic model for low-grade gliomas using translational bioinformatics

Abstract

AimsThe purpose of this study is to explore the potential biological role and prognostic significance of chromatin regulators (CRs) in low-grade gliomas (LGGs). Main methodsCRs were obtained from the FACER database. Transcription profiles of LGG patients were collected from the TCGA and CGGA databases. Differentially expressed CRs (DECRs) between LGGs and normal controls were identified using DESeq2. The consensus clustering algorithm was employed to distinguish subtypes of LGGs based on prognosis-related DECRs. The differences in clinical and molecular characteristics between different subtypes were explored. R packages, GSVA, ssGSEA, and ESTIMATE were utilized to elucidate the tumor microenvironment and activated pathways in different subtypes. Subsequently, a CRs-related signature was developed using LASSO Cox regression. Its performance was evaluated by Kaplan–Meier curve and ROC curve analyses. In vitro experiments were performed to explore the function of JADE3 in LGGs, which predominantly expressed in glioma cells. Key findingsWe identified 43 DECRs and two CRs-related subtypes of LGGs. The subtype characterized by shorter survival displayed significant enrichment for pathways associated with DNA damage response and repair, along with heightened immune cell infiltration. Furthermore, the CRs-based signature exhibited excellent prognostic performance in both the TCGA and CGGA databases. Knockdown of JADE3 significantly increased the invasion, migration, and proliferation abilities of Hs683. SignificanceOur study reveals the aberrant expression and prognostic value of CRs in LGGs. It emphasizes the potential regulatory role of CRs in the microenvironment and DNA damage repair in LGGs. JADE3 could be a possible therapeutic target for LGGs.•Two chromatin modification patterns which were closely related to the clinical and molecular characteristic of low-grade gliomas were identified.•Meanwhile, different modification patterns were also closely associated with the tumor microenvironment of low-grade gliomas.•A precise prognostic model based on seven chromatin regulators was successfully constructed and verified.•In vitro experiments had demonstrated that JADE3 could serve as an anti-oncogenic role in gliomas.