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Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

Cholesterol metabolism is involved in the progression of aggressive prostate cancer (PCa). Here the authors show that miR-205 downregulation promotes cholesterol synthesis and androgen receptor signalling in PCa through enhancing the expression of the rate-limiting enzyme of cholesterol synthesis, squalene epoxidase.

Developed using diverse sources of histopathology images, biomedical text and over 1.17 million image–caption pairs, evaluated on a suite of 14 diverse benchmarks, a visual-language foundation model achieves state-of-the-art performance on a wide array of clinically relevant pathology tasks.

X-ray study of compressed water shows that superionic ice adopts mixed close-packed structures rather than a single phase - a far more complex behaviour than expected, mirroring solid ice’s rich phases and informing planetary interior models.

Elevated expression of long noncoding RNA H19 is seen in clinical samples of neuroendocrine prostate cancer (PCa). Here the authors show H19 promotes plasticity from luminal to neuroendocrine by epigenetic reprogramming.

The components of the tumour microenvironment contribute to prostate cancer initiation and progression. Here the authors perform single-cell RNA sequencing and spatial transcriptomics analysis of prostate cancer stroma from mouse models at different stages of the disease and develop a gene signature to predict distant metastasis in patients.

Evolving over time, the Gleason scoring system has remained a crucial tool for prognosis and treatment decision making in prostate cancer. A recent study proposes a modification to the current Gleason system that should more accurately risk stratify patients and enable clinicians to make more appropriate treatment decisions.

Analyses of large population-based cohorts and clinical trials show that using polygenic scores to account for variability in PSA levels improves detection of prostate cancer, suggesting an approach for enhancing screening accuracy.

This study shows how including different ancestry groups in a genome-wide association study for prostate-specific antigen levels can improve prostate cancer risk prediction, with implications for population screening.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

A light-sheet microscope images large surgical and biopsy specimens non-destructively over large fields of view in two and three dimensions, with the same level of detail as traditional slide-based histopathology.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Here, the authors identify gene signatures tied to aggressive prostate cancer predicting poor outcomes. Further, they present data showing that early immune and metabolic shifts in normal-looking glands may signal increased relapse and metastasis risk.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

The prostate cancer tumour microenvironment in the context of treatment remains to be explored. Here, single-cell RNA-sequencing and spatial transcriptomics analysis of samples at multiple treatment points from 120 patients suggests that club-like cells may contribute to treatment resistance.

ONECUT2 is a targetable transcription factor that antagonizes androgen receptor signaling and drives androgen independence and neuroendocrine differentiation in castration-resistant prostate cancer.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Histone methyltransferase, DOTL1 is implicated in the pathogenesis of MLL-rearranged leukemia, however, not much is known of its role in prostate cancer (PCa). Here, the authors report that DOTL1 inhibition suppresses both androgen receptor and MYC pathways in a negative feed forward manner to reduce growth of AR-positive PCa.

Analysis of signatures of hypoxia in more than 8,000 tumors from 19 cancer types identifies hypoxia-driven mutation signatures and dysregulation of microRNAs.

The phenotypes of circulating tumour cells are profiled in whole blood by exploiting a microfluidic chip based on magnetic nanoparticles, leading to single-cell resolution.

Shen and colleagues find that initiation of prostate tumours by basal or luminal epithelial cells in mice leads to distinct tumour signatures. Interestingly, they find that although oncogenic transformation of basal cells gives rise to tumours with luminal phenotypes, tumours of luminal origins are more aggressive in functional tests and the distinct signature correlated with that of patients with aggressive tumours.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Pretrained using over 100,000 diagnostic histopathological slides across 20 major tissue types, a self-supervised model is shown to outperform existing baselines across various clinically relevant computational pathology tasks.

Rps genes are used to manage the major soybean pathogen Phytophthora sojae, which causes Phytophthora stem and root rot (PRR). Here, the authors show that widely used Rps genes are no longer effective for managing PRR in the United States, Canada and Argentina.

A polygenic hazard score (PHS₁) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS₂) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.