A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas

Abstract

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan–Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration–approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

Paraptosis: a unique cell death mode for targeting cancer

“…Even though being a caspase-independent form of cell death, studies by Sperandio et al (2000) have reported that caspase 9 can be an effective activator of paraptosis. In Lower-Grade Gliomas (LGG) prognostic model, ten paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to categorize LGG patients into high- and low-risk subgroups ( Qian, 2022 ).…”

Comprehensive Analysis Reveals the Potential Roles of CDKN3 in Pancancer and Verification in Endometrial Cancer

“…Previously, Mori et al thought CDKN3eRNA was a cell cycle-unassociated RNA regulator for CDKN3. 24 CDKN3 has been described as a metabolism-related gene, 67,68 a hypoxia-related gene, 69,70 a paraptosis-related gene, 71 an anti-apoptotic gene, 72 and a NO-sensitive gene, 73 Some studies have found that CDKN3 is involved in oxidative stress regulation, angiogenesis, DNA damage repair, cholesterol metabolism, fatty acid metabolism, hematopoiesis, neurocyte dendritic function regulation, and spermatogenesis. [74][75][76][77][78] Thus, CDKN3 might play a role in pathways other than the cell cycle.…”