Evidence map›Paper›PMID 39696559›Full record

ArticleCell communication and signaling : CCS2024

GG-NER's role in androgen receptor signaling inhibitor response for advanced prostate cancer.

Chuanfan Zhong, Jiaxing Wang, Hangyang Peng, Jianming Lu, Zining Long, Zhuoyuan Lin, Guo Chen, Chao Cai, Shilong Cheng, Zhongjie Chen and 4 more

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Actin-Like Protein 6A as an Oncogene and Therapeutic Target in Cancer.International journal of medical sciences · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Chuanfan Zhong *Department of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Jiaxing Wang *Department of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Hangyang Peng *Department of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Jianming LuDepartment of Andrology, Guangzhou First People's Hospital, Guangzhou Medical University, 510180, Guangzhou, Guangdong, China. louiscfc8@gmail.com.
Zining LongDepartment of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Zhuoyuan LinDepartment of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
Guo ChenDepartment of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Chao CaiDepartment of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Shilong ChengDepartment of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Zhongjie ChenDepartment of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China.
Le ZhangInstitute for Integrative Genome Biology, University of California, Riverside, California, United States.
Weibo ZhongDepartment of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China. zwbo19920709@163.com.
Rujun MoDepartment of Urology, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), 523059, Dongguan, Guangdong, China. rmo@smu.edu.cn.
Xiangming MaoDepartment of Urology, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, Guangdong, China. mxm@smu.edu.cn.

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2021B1515140069Guangzhou Science and Technology Planning Projects 202201010115National Natural Science Foundation of China 82073294National Natural Science Foundation of China 82173039National Natural Science Foundation of China 82404028
6 · The paper itself

Abstract

backgroundAdvanced prostate cancer (PCa) often initially responds to androgen receptor signaling inhibitors (ARSI) but frequently develops resistance, driven by tumor heterogeneity and therapeutic pressure. Addressing the clinical challenge of identifying non-responsive patients and discovering new therapeutic targets is urgently needed.

methodsWe utilized single-sample gene set enrichment analysis (ssGSEA) to elucidate the influence of the GG-NER pathway on ARSI response in PCa. We then constructed and validated a prognostic model based on this pathway using LASSO regression, Kaplan-Meier analysis, Cox regression, and ROC analysis. Additionally, we mapped tumor mutations to delineate the mutational landscapes across different risk groups and explored functional pathways through GO, KEGG, and GSEA analyses. The impact of the GG-NER pathway on enzalutamide sensitivity and DNA repair in PCa was further validated through CCK-8 assays, colony formation assays, in vivo experiments, and immunofluorescence.

resultsssGSEA indicated a trend of GG-NER pathway upregulation in patients with poor ARSI response. The GG-NER characteristic gene score (NECGS) identified a high-risk group with diminished ARSI response, serving as an independent prognostic indicator with strong predictive power. This high-risk group exhibited elevated TP53 mutation frequencies and significant enrichment in key pathways such as ribosome and mitochondrial functions, as well as MYC and E2F signaling. Experimental validation confirmed that targeting the GG-NER pathway or its key gene, ACTL6A, significantly reduces enzalutamide resistance in resistant cell lines and increases γH2AX expression.

conclusionNECGS effectively predicts ARSI response in PCa, and our comprehensive analysis underscores the critical role of the GG-NER pathway in enzalutamide resistance, positioning ACTL6A as a potential therapeutic target for PCa.

Indexed as

Prostatic NeoplasmsReceptors, AndrogenSignal TransductionAndrogen Receptor AntagonistsAnimalsBenzamidesCell Line, TumorDNA RepairDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansMaleMiceMutationNitrilesPhenylthiohydantoinAndrogen Receptor AntagonistsBenzamidesenzalutamideNitrilesPhenylthiohydantoinReceptors, AndrogenACTL6AARSIEnzalutamideGG-NERProstate cancer

Identifiers

PMID39696559
PMCPMC11658306

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.