Single-Cell Map of Androgen Receptor States in Resistant Prostate Cancer

Researchers in Hangzhou, China, have carried out an exploratory single-cell transcriptomic study of castration-resistant prostate cancer, examining how androgen receptor signaling is distributed across the tumor-immune microenvironment. The team, based at The First People’s Hospital of Lin’an District, reports the analysis in Frontiers in Genetics, in a study framed explicitly as hypothesis-generating rather than as proof of a new clinical marker. The work targets a long-standing problem in prostate cancer treatment.

The androgen receptor splice variant 7, known as AR-V7, has been associated in prior research with resistance to treatment in this setting, yet its relationship with the immune landscape of tumors remains incompletely defined. To probe that interface, the researchers performed a secondary analysis of the publicly available single-cell RNA sequencing dataset GSE137829, which contains castration-resistant prostate cancer samples. Their computational pipeline used Seurat-based preprocessing, dimensionality reduction, cell type annotation, trajectory inference, SCENIC regulatory network analysis, pathway enrichment, and CellPhoneDB.

The single-cell data revealed substantial heterogeneity within the tumors, spanning epithelial, immune, and stromal compartments. According to the authors, the dataset supported analysis of androgen receptor-associated transcriptional states and candidate regulatory programs across these cell populations, offering a map of the cellular diversity that characterizes advanced prostate cancer at single-cell resolution. A key methodological limitation shaped the study’s scope.

The public dataset does not provide validated AR-V7 status at either the patient or the single-cell level. The team therefore did not use the data to classify tumors or cells as AR-V7-positive versus AR-V7-negative, avoiding a comparison the underlying data could not support. As a supportive analysis, the researchers turned to laboratory measurements in two prostate cancer cell lines, 22Rv1 and LNCaP.

Reverse transcription quantitative polymerase chain reaction, or RT-qPCR, showed higher expression of the genes KLK3, STEAP2, HOXB13, and NKX3-1 in 22Rv1 cells than in LNCaP cells. The authors are careful about what this comparison shows. They interpret the expression differences as supportive AR-associated observations rather than as AR-V7-specific mechanistic validation.

In other words, the cell line data are consistent with differences in androgen receptor pathway activity between the two lines, but they do not by themselves demonstrate that AR-V7 drives the observed pattern or that the same relationships hold in patient tumors. The study’s conclusions are correspondingly restrained. The authors describe the work as an exploratory transcriptomic characterization of androgen receptor-associated cellular states in castration-resistant prostate cancer.

They state that the findings do not establish AR-V7-specific causality and do not provide clinical prediction, positioning the results as a starting point for further investigation rather than a diagnostic or prognostic tool. What the study does deliver is a detailed single-cell view of the cellular composition and androgen receptor-linked transcriptional programs within castration-resistant prostate cancer, together with cell-line measurements that point toward candidate genes for follow-up.

The authors identify the next steps clearly: functional perturbation studies, in which AR-V7 or related pathways are experimentally manipulated, and datasets in which AR-V7 status is directly measured, will be required to test whether the associations observed here reflect causal mechanisms relevant to treatment resistance. Until such studies are completed, the single-cell map and the supportive RT-qPCR observations stand as hypothesis-generating results that outline where future research on the androgen receptor-tumor-immune interface in castration-resistant prostate cancer should look next.

Subject of Research: Single-cell transcriptomic analysis of androgen receptor signaling in castration-resistant prostate cancer

Article Title: Androgen receptor signaling at the tumor-immune interface in castration-resistant prostate cancer: single-cell transcriptomic analysis with AR-V7-related RT-qPCR context

Article References: Guo, C., Wu, L., & Xu, L. (2026). Androgen receptor signaling at the tumor-immune interface in castration-resistant prostate cancer: single-cell transcriptomic analysis with AR-V7-related RT-qPCR context. Frontiers in Genetics, 17, Article 1945967. https://doi.org/10.3389/fgene.2026.1945967

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1945967

Keywords: androgen receptor, AR-V7, castration-resistant prostate cancer, single-cell RNA sequencing, RT-qPCR, tumor microenvironment, Androgen, receptor, signaling, tumor-immune, interface, castration-resistant