Biology subjects

Semmes, O. J.

Publications and source records attributed to Semmes, O. J..

4 recordsLinked to original sources

bioRxiv2025

Ancestry-Dependent Immunologic and Prognostic Effects Characterize the Prostate Cancer Urinary Proteome

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individuals urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between these groups after controlling for age, PSA, and cISUP. Immune pathways were particularly dysregulated. The urinary proteome of Black patients harboured more features of aggressive cancers than those of grade- and PSA-matched White patients. These observations highlight the importance of controlling for race- and ancestry-associated differences in the development of urinary biomarkers.

cancer biology↗

bioRxiv2024

PROSTATE CELL HETEROGENEITY AND CXCL17 UPREGULATION IN MOUSE STEROID HORMONE IMBALANCE

Benign prostatic hyperplasia (BPH) is a prevalent age-related condition often characterized by debilitating urinary symptoms. Its etiology is believed to stem from hormonal imbalance, particularly an elevated estradiol-to-testosterone ratio and chronic inflammation. Our previous studies using a mouse steroid hormone imbalance model identified a specific increase in macrophages that migrate and accumulate in the prostate lumen where they differentiate into lipid-laden foam cells in mice implanted with testosterone and estradiol pellets, but not in sham animals. The current study focused on further characterizing the cellular heterogeneity of the prostate in this model as well as identifying the specific transcriptomic signature of the recruited foam cells. Moreover, we aimed to identify the epithelia-derived signals that drive macrophage infiltration and luminal translocation. Male C57BL/6J mice were implanted with slow-release testosterone and estradiol pellets (T+E2) and harvested the ventral prostates two weeks later for scRNA-seq analysis, or performed sham surgery. We identified Ear2+ and Cd72+ macrophages that were elevated in response to steroid hormone imbalance, whereas a Mrc1+ resident macrophage population did not change. In addition, an Spp1+ foam cell cluster was almost exclusively found in T+E2 mice. Further markers of foam cells were also identified, including Gpnmb and Trem2, and GPNMB was confirmed as a novel histological marker with immunohistochemistry. Foam cells were also shown to express known pathological factors Vegf, Tgfb1, Ccl6, Cxcl16 and Mmp12. Intriguingly, a screen for chemokines identified the upregulation of epithelial-derived Cxcl17, a known monocyte attractant, in T+E2 prostates suggesting that it might be responsible for the elevated macrophage number as well as their translocation to the lumen. Our study identified macrophage subsets that respond to steroid hormone imbalance as well as further confirmed a potential pathological role of luminal foam cells in the prostate. These results underscore a pathological role of the identified prostate foam cells and suggests CXCL17-mediated macrophage migration as a critical initiating event.

pathology↗

bioRxiv2023

Prostate Cancer Reshapes the Secreted and Extracellular Vesicle Urinary Proteomes

Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine. Secreted and EV proteins arise from different subcellular compartments. Urinary EVs are faithful surrogates of tissue proteomes, but secreted proteins in urine or cell line EVs are not. The urinary proteome is longitudinally stable over several years. It can accurately and non-invasively distinguish malignant from benign prostatic lesions, and can risk-stratify prostate tumors. This resource quantifies the complexity of the urinary proteome, and reveals the synergistic value of secreted and EV proteomes for translational and biomarker studies.

systems biology↗

bioRxiv2022

promor: a comprehensive R package for label-free proteomics data analysis and predictive modeling

SummaryWe present promor, a comprehensive, user-friendly R package that streamlines label-free (LFQ) proteomics data analysis and building machine learning-based predictive models with top protein candidates. Availability and implementationpromor is freely available as an open source R package on the Comprehensive R Archive Network (CRAN)(https://CRAN.R-project.org/package=promor) and distributed under the Lesser General Public License (version 2.1 or later). Development version of promor is maintained on GitHub (https://github.com/caranathunge/promor) and additional documentation and tutorials are provided on the package website (https://caranathunge.github.io/promor/). Contactcaranathunge86@gmail.com

bioinformatics↗