A PARP1-related prognostic signature constructing and PARP-1 inhibitors screening for glioma.

in Frontiers in cell and developmental biology by Hui Li, Zhenhua Wang, Yuanyuan Hou, Jianxin Xi, Zhenqiang He, Han Lu, Zhishan Du, Sheng Zhong, Qunying Yang

TLDR

  • TLDR: PARP-1 is a DNA repair protein overactive in glioma tumors. Inhibiting PARP-1 could improve treatment outcomes for glioma patients.
  • Key Insights: The study found that PARP-1 is a potential target for glioma therapy, and lower PARP-1 activity is associated with better prognosis.

Abstract

The current standard treatments of glioma include surgical resection, supplemented with radiotherapy and chemotherapy, but the prognosis is poor. PARP-1 (Poly ADP-ribose polymerase 1) is a hot spot for cancer-targeted therapy and was reported to be significantly elevated in glioma. In this study, we analyzed the role of PARP-1 in DNA damage repair, constructed a PARP1-related DNA-repair prognostic signature (DPS), and screened targeted drugs for glioma. RNA-seq data of 639 glioma samples were downloaded from the GEO (Gene Expression Omnibus) database and divided into PARP1_H and PARP1_L according to the front and rear thirds of the expression level of PARP-1. First, we systematically analyzed the influence of PARP-1 on DNA damage repair, prognosis, and chemoradiotherapy sensitization of glioma. All glioma patients and patients with radiotherapy or chemotherapy had a better prognosis in PARP1_L than in PARP1_H. Next, differentially expressed DNA-repair related genes (DEGs) were identified between PARP1_H and PARP1_L by LASSO (Least Absolute Shrinkage and Selection Operator) Cox analysis and applied for constructing DPS. Based on the four-gene DPS, we then developed a new nomogram to assess overall survival in glioma patients. Additionally, PARP-1 was proved an effective target for glioma therapy. So, a series of computer-aided techniques, including Discovery Studio 4.5, Schrodinger, and PyMol, were applied for the virtual screening of favorable PARP-1 inhibitors. In conclusion, this study investigated the effect of PARP-1 on glioma prognosis and the sensitization effect of radiotherapy and chemotherapy, established a novel nomogram to evaluate the overall survival of glioma patients, and further explored targeted therapy for glioma.

Overview

  • The study aimed to investigate the role of PARP-1 in glioma prognosis and sensitization to radiotherapy and chemotherapy.
  • The researchers analyzed RNA-seq data of 639 glioma samples and divided them into PARP1_H and PARP1_L based on the expression level of PARP-1.
  • The primary objective was to develop a PARP1-related DNA-repair prognostic signature (DPS) and screen targeted drugs for glioma therapy.

Comparative Analysis & Findings

  • The study found that glioma patients with lower PARP-1 expression (PARP1_L) had a better prognosis than those with higher PARP-1 expression (PARP1_H).
  • Differentially expressed DNA-repair related genes (DEGs) were identified between PARP1_H and PARP1_L, which were used to construct the PARP1-related DNA-repair prognostic signature (DPS).
  • The DPS was used to develop a new nomogram to assess overall survival in glioma patients, which showed good diagnostic accuracy.

Implications and Future Directions

  • The study suggests that PARP-1 is an effective target for glioma therapy, and its inhibition could improve the efficacy of radiotherapy and chemotherapy.
  • Future studies could investigate the use of PARP-1 inhibitors in combination with other therapies to enhance treatment outcomes for glioma patients.
  • The development of a nomogram to assess overall survival in glioma patients has the potential to improve personalized treatment decisions and patient outcomes.
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