Prognostic implication of heterogeneity and trajectory progression induced by enzalutamide in prostate cancer

作者：Yuanfa Feng, Yulin Deng, Zhenfeng Tang, Shanghua Cai, Jinchuang Li, Ren Liu, Jiaming Wan, Huichan He, Guohua Zeng, Jianheng Ye, Zhaodong Han, Weide Zhong · 发表于：Frontiers in Endocrinology · 年份：2023 · DOI：10.3389/fendo.2023.1148898 · 被引用次数：5 · 研究领域：Prostate Cancer Treatment and Research、Ferroptosis and cancer prognosis、Single-cell and spatial transcriptomics

Background: Enzalutamide, as a second-generation endocrine therapy drug for prostate cancer (PCa), is prominent representative among the synthetic androgen receptor antagonists. Currently, there is lack of enzalutamide-induced signature (ENZ-sig) for predicting progression and relapse-free survival (RFS) in PCa. Methods: Enzalutamide-induced candidate markers were derived from single-cell RNA sequencing analysis integrating three enzalutamide-stimulated models (0-, 48-, and 168-h enzalutamide stimulation). ENZ-sig was constructed on the basis of candidate genes that were associated with RFS in The Cancer Genome Atlas leveraging least absolute shrinkage and selection operator method. The ENZ-sig was further validated in GSE70768, GSE94767, E-MTAB-6128, DFKZ, GSE21034, and GSE70769 datasets. Biological enrichment analysis was used to discover the underlying mechanism between high ENZ-sig and low ENZ-sig in single-cell RNA sequencing and bulk RNA sequencing. Results: We identified a heterogenous subgroup that induced by enzalutamide stimulation and found 53 enzalutamide-induced candidate markers that are related to trajectory progression and enzalutamide-stimulated. The candidate genes were further narrowed down into 10 genes that are related to RFS in PCa. A 10-gene prognostic model (ENZ-sig)-IFRD1, COL5A2, TUBA1A, CFAP69, TMEM388, ACPP, MANEA, FOSB, SH3BGRL, and ST7-was constructed for the prediction of RFS in PCa. The effective and robust predictability of ENZ-sig was verifie...