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Integrative single-cell and spatial transcriptomics with explainable AI reveal lethal prognostic axis in prostate cancer 期刊论文

编号：

0B3688265ECAD3AA9D2C85E4276FA3EF
作者：

Ge, Qintao#^[1,2,3,4]Wang, Zhenda^[1,2];Wang, Yangyun^[5];Chu, Tonghui^[1,2];Wang, Zhongyuan^[3,4];Zhu, Wenkai^[6];Zhang, Youzhao^[1,2];Chen, Yonghao^[7];Ye, Dingwei*^[3,4]Xu, Wenhao*^[3,4]Wang, Zhong*^[1,2]Abudurexiti, Mierxiati*^[1,2]
语种：

英文
期刊：

NPJ DIGITAL MEDICINE ISSN：2398-6352 2026 年 9 卷 1 期 ; JAN 6
收录：
摘要：

Prostate cancer (PCa) remains clinically heterogeneous. We integrated single-cell and spatial transcriptomics with explainable machine learning to define a lethal tumor axis and establish an interpretable prognostic model. From 141,986 high-quality single cells spanning localized, hormone-sensitive, and castration-resistant PCa, we identified a malignant C4 epithelial subpopulation characterized by high chromosomal instability, androgen receptor and cell-cycle activation, and stemness potential. Spatial mapping further revealed immune-enriched yet suppressive niches, where fibroblasts and myeloid cells coexisted with exhausted lymphocytes, reflecting functional immune imbalance. We benchmarked 101 machine learning pipelines, selecting a Lasso plus PLS-Cox model that achieved strong concordance across independent cohorts. The C4-based risk score independently predicted recurrence-free survival after adjustment for age, Gleason score and T stage, and a nomogram combining this score with clinical variables showed good discrimination. SHAP interpretation highlighted MT1M, PCSK1N, and ACSL3 as major risk-driving features. PCSK1N was progressively upregulated from normal prostate to castration-resistant disease and promoted proliferation, clonogenicity, migration and enzalutamide resistance, while its inhibition sensitized organoids and xenografts to AR-targeted therapy. These findings define a C4-centered lethal tumor axis and provide an explainable, experimentally supported framework for prognostic stratification in PCa.
推荐引用方式
GB/T 7714：

Ge Qintao,Wang Zhenda,Wang Yangyun, et al. Integrative single-cell and spatial transcriptomics with explainable AI reveal lethal prognostic axis in prostate cancer [J].NPJ DIGITAL MEDICINE,2026,9(1).
APA：

Ge Qintao,Wang Zhenda,Wang Yangyun,Chu Tonghui,&Abudurexiti Mierxiati.(2026).Integrative single-cell and spatial transcriptomics with explainable AI reveal lethal prognostic axis in prostate cancer .NPJ DIGITAL MEDICINE,9(1).
MLA：

Ge Qintao, et al. "Integrative single-cell and spatial transcriptomics with explainable AI reveal lethal prognostic axis in prostate cancer" .NPJ DIGITAL MEDICINE 9,1(2026).
入库时间：

2/16/2026 9:18:56 PM
更新时间：

2/16/2026 9:18:56 PM

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