Biomedical subjects

Jessica Hicks

Publications and source records attributed to Jessica Hicks.

3 recordsLinked to original sources

PubMed2026

A transition zone enriched WIF1+ basal cell subtype is associated with benign prostatic hyperplasia.

The cellular composition and disease susceptibilities of the distinct zones of the human prostate remain incompletely understood. Benign prostatic hyperplasia (BPH) is a common condition that causes widespread morbidity and is nearly exclusively localized to the transition zone (TZ). Through extensive single-cell RNA sequencing (scRNA-seq) of benign regions from prostatectomy specimens, we identified a basal cell population expressing WIF1, VCAN, and NRG1, among other genes, that was significantly enriched in the TZ. Analysis of previously published scRNA-seq datasets further confirmed that WIF1+ basal cells were significantly enriched in BPH compared with normal prostate. Pathway and cell-cell communication analyses revealed that this basal subtype is associated with programs related to cell proliferation, epithelial-mesenchymal transition, immune regulation, angiogenesis, and hormone response. Together, the molecular signature, zonal distribution, and pathway enrichment suggest that TZ-enriched WIF1+ basal cells may contribute to BPH pathogenesis by promoting epithelial and stromal remodeling. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

NRG1↗

PubMed2026

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with ≥pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities↗

PubMed2026

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations with Race and Prostate Cancer Outcomes.

BACKGROUND: Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer. Herein we evaluate the prevalence of intratumoral (subclonal) complete p27 protein loss (IPPL) in primary prostate cancer. EXPERIMENTAL DESIGN: We used immunohistochemistry (IHC) for p27 in a large cohort of whole tissue sections from radical prostatectomy (n=412) and metastases from self-identified African American (AA) and European American (EA) individuals. IPPL was evaluated alongside CDKN1B mRNA in-situ hybridization and next generation sequencing of laser captured cancer regions. Cox proportional hazards analyses assessed the association of IPPL with biochemical recurrence and development of metastases after radical prostatectomy. RESULTS: IPPL was detected in 18.1% of AA versus 12.2% of EA cases and was tightly correlated with CDKN1B mRNA loss and biallelic genomic loss. IPPL was associated with ≥pT3 pathologic stage and pN1 disease, however these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available datasets as well as our analysis of autopsy cases via IHC, indicating that complete p27 loss may be selected for in metastatic disease. CONCLUSIONS: Subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer, and could contribute to worse prostate cancer outcomes, specifically in AA males.

Journal Article↗