Extracellular Domain Shedding of TROP2 Activates EGFR Signaling to Drive Prostate Cancer Metastasis.

Metastasis is the main cause of prostate cancer-associated deaths, highlighting the urgent need to determine the mechanisms underlying prostate cancer progression. TROP2 (also known as TACSTD2) is an oncogenic transmembrane surface protein that is highly expressed in metastatic prostate cancer. Naturally occurring cleavage of TROP2 leads to a release of the TROP2 extracellular domain (TECD) into the extracellular environment.

The RNA demethylase FTO promotes glutamine metabolism in clear cell renal cell carcinoma through the regulation of SLC1A5.

Glutamine reprogramming plays a crucial role in the growth and survival of clear cell renal cell carcinoma (ccRCC), although the mechanisms governing its regulation are still not fully understood. We demonstrate that the RNA demethylase fat mass and obesity-associated gene (FTO) drives glutamine reprogramming to support ccRCC growth and survival. Genetic and pharmacologic inhibition of FTO in ccRCC cells impaired glutamine-derived reductive carboxylation, depleted pyrimidines, and increased reactive oxygen species.

Magnetic Resonance Imaging at Second Surveillance Biopsy After Diagnosis in Patients With Grade Group 1 Prostate Cancer in the Canary Prostate Active Surveillance Study.

Purpose: No clear guidelines exist regarding MRI use after confirmatory biopsy during active surveillance. Our objective was to evaluate MRI performance after confirmatory biopsy in patients with vs without prior MRI-informed biopsy.

Materials And Methods: Patients in the Canary Prostate Active Surveillance Study with Gleason Grade Group (GG) 1 disease undergoing MRI-informed Biopsy 2, defined as second surveillance biopsy after diagnosis, were separated into prior vs no prior MRI-informed biopsy groups.

Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics.

: Clear-cell renal cell carcinoma (ccRCC) is a heterogenous disease that can be classified into multiple molecular subtypes with differential prognosis and sensitivities to treatments based on their genomic, transcriptomic, proteomic, and metabolic profiles. Patient-derived xenografts (PDXs) are high-fidelity cancer models because they maintain similar genotypes and immunohistologic phenotypes to the parental tumors and respond to standard-of-care therapies as expected. However, whether the molecular subtypes identified in ccRCC patient samples are preserved in PDX models is not clear.

Associations Between Prostate Cancer and Dementia: A Nationwide Study in Sweden.

Background And Objective: Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.

Methods: To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998-2017 and 1 787 460 age-matched control men in Sweden without prior dementia.

Immune repertoire profiling uncovers pervasive T cell clonal expansions in benign prostatic hyperplasia.

We discovered T-cell clonal expansions in benign prostatic hyperplasia, indicative of a specific adaptive immune response and with implications for disease pathogenesis and new treatments.

The olfactory receptor OR51E2 regulates prostate cancer aggressiveness and modulates STAT3 in prostate cancer cells and in xenograft tumors.

Background: Despite advancements in the detection and treatment of prostate cancer, the molecular mechanisms underlying its progression remain unclear. This study aimed to investigate the role of the receptor OR51E2, which is commonly upregulated in prostate cancer, in the progression of this disease.

Methods: We investigated the physiological effects of OR51E2 through CRISPR-Cas9-induced monoclonal OR51E2 knockout.

Intact glycopeptide analysis of human prostate tissue reveals site-specific heterogeneity of protein glycosylation in prostate cancer.

Approximately 300,000 American men were diagnosed with prostate cancer in 2024. Existing screening approaches based on measuring levels of prostate-specific antigen in the blood lack specificity for prostate cancer. Studying the glycans attached to proteins has the potential to generate new biomarker candidates and/or increase the specificity of existing protein biomarkers, and studying protein glycosylation changes in prostate cancer could also add new information to our understanding of prostate cancer biology.

Targeting AXL Inhibits the Growth and Metastasis of Prostate Cancer in Bone.

Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in prostate cancer and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.

Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by IHC staining.

Aggressiveness classification of clear cell renal cell carcinoma using registration-independent radiology-pathology correlation learning.

Background: Renal cell carcinoma (RCC) is a common cancer that varies in clinical behavior. Clear cell RCC (ccRCC) is the most common RCC subtype, with both aggressive and indolent manifestations. Indolent ccRCC is often low-grade without necrosis and can be monitored without treatment.

Sialylated glycoproteins suppress immune cell killing by binding to Siglec-7 and Siglec-9 in prostate cancer.

Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer.

Risk of anxiety disorders in men with prostate cancer: a national cohort study.

Background: Men with prostate cancer (PC) may experience significant psychosocial distress from physical symptoms, treatment side effects, or fear of recurrence. However, little is known about the long-term risk of anxiety disorders in men with PC.

Methods: A national cohort study was conducted of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched population-based control men in Sweden.

Establishing and Characterizing the Molecular Profiles, Cellular Features, and Clinical Utility of a Patient-Derived Xenograft Model Using Benign Prostatic Tissues.

Benign prostatic hyperplasia (BPH) is a common condition marked by the enlargement of the prostate gland, which often leads to significant urinary symptoms and a decreased quality of life. The development of clinically relevant animal models is crucial for understanding the pathophysiology of BPH and improving treatment options. This study aims to establish a patient-derived xenograft (PDX) model using benign prostatic tissues to explore the molecular and cellular mechanisms of BPH.

Assessing sociodemographic and regional disparities in Oncotype DX Genomic Prostate Score uptake.

Background: The Oncotype DX Genomic Prostate Score (ODX-GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX-GPS uptake.

Methods: Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3 + 3 or 3 + 4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX-GPS data.

Upgrading of Grade Group 1 Prostate Cancer at Prostatectomy: Germline Risk Factors in a Prospective Cohort.

Background: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic, and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery.

Incidence and Pitfalls of Adipose Tissue Encountered in Prostatic Transurethral Resections and Related Specimens.

While the presence of adipose tissue and its involvement by prostatic cancer (extraprostatic extension) is well-recognized in prostate biopsies, adipose tissue in transurethral resections of the prostate (TURP) is largely unexplored. Herein, 200 consecutive TURPs and related specimens were reviewed, including a separate 3-year analysis of specimens containing prostatic cancer, with the following data collected: presence of fat, presence of cancer within fat, and quantity of fat. For specimens with both fat and prostatic cancer, specimen weight and tumor volume were recorded.

Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer.

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making.

Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort.

Design, Setting, And Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

Background: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive.

Mortality Risks Associated with Depression in Men with Prostate Cancer.

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

RAPHIA: A deep learning pipeline for the registration of MRI and whole-mount histopathology images of the prostate.

Image registration can map the ground truth extent of prostate cancer from histopathology images onto MRI, facilitating the development of machine learning methods for early prostate cancer detection. Here, we present RAdiology PatHology Image Alignment (RAPHIA), an end-to-end pipeline for efficient and accurate registration of MRI and histopathology images. RAPHIA automates several time-consuming manual steps in existing approaches including prostate segmentation, estimation of the rotation angle and horizontal flipping in histopathology images, and estimation of MRI-histopathology slice correspondences.

Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

Background: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer.

Identification and characterization of intact glycopeptides in human urine.

Glycoproteins in urine have the potential to provide a rich class of informative molecules for studying human health and disease. Despite this promise, the urine glycoproteome has been largely uncharacterized. Here, we present the analysis of glycoproteins in human urine using LC-MS/MS-based intact glycopeptide analysis, providing both the identification of protein glycosites and characterization of the glycan composition at specific glycosites.