Evidence map›Paper›PMID 39033192›Full record

ArticleEuropean journal of medical research2024

Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma.

Junjie Zhao, Xiuyi Pan, Zilin Wang, Yuntian Chen, Dingbang Liu, Yu Shen, Xinyuan Wei, Chenhao Xu, Xingming Zhang, Xu Hu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. PHLDA2 in cancer: From molecular mechanisms to therapeutic opportunities.The Journal of pharmacology and experimental therapeutics · 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

18 authors.

Junjie Zhao *Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Xiuyi Pan *Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Zilin Wang *Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Yuntian ChenDepartment of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Dingbang LiuDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Yu ShenDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Xinyuan WeiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Chenhao XuDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Xingming ZhangDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Xu HuDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Junru ChenDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Jinge ZhaoDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Bo TangDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Guangxi SunDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Pengfei ShenDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China.
Zhenhua Liu *Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China. Zhenhuazhliu@scu.edu.cn.
Hao Zeng *Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China. kucaizeng@163.com.
Jiayu Liang *Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China. jiayu.liang@scu.edu.cn.

Funding

China Postdoctoral Science Foundation 2021M692281China Postdoctoral Science Foundation 2021M702344Sichuan Province Science and Technology Support Program 2022YFS0305The Natural Science Foundation of China NSFC82202901The Natural Science Foundation of China NSFC82203280The Natural Science Foundation of China NSFC82373422The Natural Science Foundation of Sichuan Province 2023NSFSC1856
6 · The paper itself

Abstract

backgroundA substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown.

methodsTranscriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation.

resultsMembers of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed.

conclusionsOur study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.

Indexed as

Carcinoma, Renal CellEpigenesis, GeneticImmune Checkpoint InhibitorsKidney NeoplasmsNuclear ProteinsTumor MicroenvironmentBiomarkers, TumorDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansMalePrognosisBiomarkers, TumorImmune Checkpoint InhibitorsNuclear ProteinsTSSC3 proteinBiomarkerClear cell renal cell carcinomaDNA hypomethylationImmune checkpoint inhibitorImmune microenvironmentPHLDA2

Identifiers

PMID39033192
PMCPMC11264912

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.