Multi-cohort screening of PANoptosis-related genes reveals PARP1 as a key target, and AZD5305 exerts anti-tumor effects in neuroblastoma
4 affiliations
- 1Department of Urology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, the Laboratory of Targeted Delivery of Traditional Chinese Medicine, Chongqing, China
- 2Department of anesthesiology, Children’s Hospital of Chongqing Medical University, Chongqing, China
- 3The Second Affiliated Hospital of Chongqing Medical University, Key Laboratory of Integrated Therapy of Traditional Chinese Medicine for Tumors, Chongqing Municipal Administration of Traditional Chinese Medicine, Chongqing, China
- 4Department of Pediatrics, The Second Clinical College of Chongqing Medical University, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Abstract
Background: Neuroblastoma (NB) is the most prevalent extracranial solid malignant tumor in infants and children. Approximately half of children with high-risk NB exhibit primary resistance to first-line therapy or experience disease relapse within two years post-treatment, leading to dismal overall survival. PANoptosis is an inflammatory programmed cell death modality integrating pyroptosis, apoptosis and necroptosis; nevertheless, the functional relevance of PANoptosis-related genes (PRGs) in NB remains largely undefined. This study aimed to explore PRGs associated with NB prognosis and their link to the tumor immune microenvironment, so as to identify novel therapeutic targets for NB.
Methods: mRNA expression profiles from three public NB datasets (GSE49711-NB, TARGET-NB and E-MTAB-8248-NB) were used to investigate the prognostic roles of 19 previously reported PRGs. Independent Cox regression screening was performed in each cohort to identify cohort-specific prognostic PRGs, followed by Venn intersection analysis to identify conserved prognostic genes. PARP1 expression was validated in tumor tissues from 127 clinical NB patients. The GIS score based on PARP1 expression and clinical metadata were combined to assess its prognostic value. In vitro functional assays were performed to explore the anti-tumor effects and mechanisms of the PARP1 inhibitor AZD5305.
Results: Venn intersection analysis identified PARP1 as the only shared gene with consistent prognostic significance across heterogeneous NB patient populations. In vitro experiments revealed that AZD5305 markedly suppressed NB cell proliferation, migration and invasion, triggered cell apoptosis, and arrested cell cycle progression at the G0/G1 phase.
Conclusion: This study adopts a multi-cohort parallel screening strategy to mine conserved therapeutic targets for NB. Our data indicate that PARP1 inhibition via AZD5305 represents a promising therapeutic strategy for NB treatment.
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BibTeX
@article{shi2026multicohort,
title = {{Multi-cohort screening of PANoptosis-related genes reveals PARP1 as a key target, and AZD5305 exerts anti-tumor effects in neuroblastoma}},
author = {Shujun Shi and Zhaoxia Zhang and Junyi Luo and Zhaoying Wang and Tao Mi and Liming Jin and Xiangpan Kong and Jinkui Wang and Junhong Liu and Li Wang and Dawei He},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1903085},
url = {https://doi.org/10.3389/fonc.2026.1903085},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-cohort screening of PANoptosis-related genes reveals PARP1 as a key target, and AZD5305 exerts anti-tumor effects in neuroblastoma
AU - Shujun Shi
AU - Zhaoxia Zhang
AU - Junyi Luo
AU - Zhaoying Wang
AU - Tao Mi
AU - Liming Jin
AU - Xiangpan Kong
AU - Jinkui Wang
AU - Junhong Liu
AU - Li Wang
AU - Dawei He
PY - 2026
DA - 2026/10/12
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1903085
UR - https://doi.org/10.3389/fonc.2026.1903085
AB - Background: Neuroblastoma (NB) is the most prevalent extracranial solid malignant tumor in infants and children. Approximately half of children with high-risk NB exhibit primary resistance to first-line therapy or experience disease relapse within two years post-treatment, leading to dismal overall survival. PANoptosis is an inflammatory programmed cell death modality integrating pyroptosis, apoptosis and necroptosis; nevertheless, the functional relevance of PANoptosis-related genes (PRGs) in NB remains largely undefined. This study aimed to explore PRGs associated with NB prognosis and their link to the tumor immune microenvironment, so as to identify novel therapeutic targets for NB. Methods: mRNA expression profiles from three public NB datasets (GSE49711-NB, TARGET-NB and E-MTAB-8248-NB) were used to investigate the prognostic roles of 19 previously reported PRGs. Independent Cox regression screening was performed in each cohort to identify cohort-specific prognostic PRGs, followed by Venn intersection analysis to identify conserved prognostic genes. PARP1 expression was validated in tumor tissues from 127 clinical NB patients. The GIS score based on PARP1 expression and clinical metadata were combined to assess its prognostic value. In vitro functional assays were performed to explore the anti-tumor effects and mechanisms of the PARP1 inhibitor AZD5305. Results: Venn intersection analysis identified PARP1 as the only shared gene with consistent prognostic significance across heterogeneous NB patient populations. In vitro experiments revealed that AZD5305 markedly suppressed NB cell proliferation, migration and invasion, triggered cell apoptosis, and arrested cell cycle progression at the G0/G1 phase. Conclusion: This study adopts a multi-cohort parallel screening strategy to mine conserved therapeutic targets for NB. Our data indicate that PARP1 inhibition via AZD5305 represents a promising therapeutic strategy for NB treatment.
SN - 2234-943X
ER -