Evidence map›Paper›PMID 42393527›Full record

ArticleMolecular medicine (Cambridge, Mass.)2026

Low-PSMA hormone-sensitive prostate cancer: a distinct clinical and molecular state.

Haotian Wu, Ang Li, Zhou Jiang, Weiwei Zhang, Kai Shen, Bo Liu, Ruopeng Su, Xinyu Liu, Xinyu Chai, Tianxiang Wang and 8 more

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Haotian Wu *Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ang Li *Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhou Jiang *Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weiwei ZhangDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kai ShenDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bo LiuDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ruopeng SuDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinyu LiuDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinyu ChaiDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tianxiang WangDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Junyi WangDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiayan YiDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiang ZhouDepartment of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yinjie ZhuDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dengfeng CaoDepartment of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qi WangDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wqi@sjtu.edu.cn.
Jiahua PanDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jiahua.pan@outlook.com.
Wei XueDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xuewei@renji.com.

Funding

China Postdoctoral Science Foundation 2025M772209National Natural Science Foundation of China 82373358Renji Hospital RJLJHZ-02Ren Ji Hospital LYZXHXKT220845Shanghai Higher Education Society Research Project 2QYB24089Shanghai Municipal Education Commission Grant Support 2023ZKZD23The Explorers Program of Shanghai 25TS1403800
6 · The paper itself

Abstract

backgroundA subset of hormone-sensitive prostate cancer (HSPC) exhibits low prostate-specific membrane antigen (PSMA) uptake on PET imaging, which may limit the performance of PSMA-based detection and PSMA-directed therapeutic strategies. However, the clinical features and molecular basis of HSPC with low PSMA expression remain incompletely defined.

methodsWe first analyzed a retrospective dual-tracer PET cohort to estimate the frequency and clinical characteristics of tumors with low PSMA uptake at initial diagnosis. We then collected radical prostatectomy specimens for proteomics profiling, classifying tumors as low-PSMA (N = 16) or high-PSMA (N = 19) based on concordant [

resultsLow-PSMA HSPC was identified in 7.23% (122/1,688) of patients in the retrospective dual-tracer PET cohort, indicating that reduced PSMA uptake is already observable at initial diagnosis. Although these tumors showed reduced PSMA expression, they were not uniformly low-risk, with 42.62% of cases exhibiting Gleason score ≥ 8. In the proteomic cohort, low-PSMA tumors showed concordant reductions in PSMA uptake and protein expression, supporting imaging-pathology alignment. Proteomic analysis revealed a distinct molecular state characterized by enrichment of tissue remodeling, repair, epithelial organization, and microenvironment-related programs, together with attenuation of androgen-response, E2F, and MYC-associated proliferative signaling. Cell-surface membrane surface target prioritization identified ALCAM and TACSTD2 as candidates, among which ALCAM was consistently upregulated in low-PSMA tumors at both mRNA and protein levels.

conclusionsHSPC with low PSMA expression represents a distinct clinical and molecular state rather than a simple low-risk subgroup. Its proteomic features suggest altered epithelial differentiation, tissue remodeling, and reduced canonical prostate cancer signaling. ALCAM may serve as a complementary membrane biomarker for improving the molecular recognition of low-PSMA HSPC and supporting future alternative imaging or targeting strategies.

Indexed as

Antigens, SurfaceGlutamate Carboxypeptidase IIProstatic NeoplasmsAgedBiomarkers, TumorHumansMalePositron-Emission TomographyProteomicsRetrospective StudiesAntigens, SurfaceBiomarkers, TumorFOLH1 protein, humanGlutamate Carboxypeptidase IIHormone-sensitive Prostate CancerProstate-specific Membrane AntigenProteomic AnalysisTumor Biomarker

Identifiers

PMID42393527
PMCPMC13599339

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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.