Analysis of Divergent Gene Expression between HPV+ and HPV- Head and Neck Squamous Cell Carcinoma Patients DOI Creative Commons
Kasturika Shankar, Sarah E. Walker

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract Human Papillomavirus (HPV) is a non-enveloped virus with circular double-stranded DNA genome. It one of the most common sexually transmitted infections, high-risk types such as HPV-16 and HPV-18 linked to anogenital head neck squamous cell carcinomas (HNSCC). HNSCC includes cancers oral cavity, pharynx, larynx, related regions, caused by carcinogens or persistent viral infections. HPV-positive (HPV+) cases are more prevalent in Western countries exhibit better prognosis treatment response compared HPV-negative (HPV-) cases. These differences suggest distinct fundamental between each subtype. This study analyzed RNA-seq data from PanCancer Atlas 2018 dataset investigate molecular distinctions HPV+ HPV-HNSCC. Using dimensionality reduction techniques Principal Component Analysis (PCA) Uniform Manifold Approximation Projection (UMAP), clear clustering was observed, suggesting unique gene expression profile. tumors exhibited upregulation genes involved nucleic acid processing downregulation associated apoptosis epidermis development. findings underscore biological HPV-HNSCC, offering insights into HPV-driven oncogenesis. Understanding these may improve patient stratification inform targeted therapeutic strategies for HNSCC.

Language: Английский

Unraveling the YAP1-TGFβ1 axis: a key driver of androgen receptor loss in prostate cancer-associated fibroblasts DOI Creative Commons
Edward Brunner, Elisabeth Damisch,

Melanie Emma Groninger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Abstract Due to their pivotal roles in tumor progression and therapy resistance, cancer-associated fibroblasts (CAF) are considered key therapeutic targets with loss of stromal androgen receptor (AR) a poorly understood hallmark aggressive prostate cancer (PCa). A paucity pre-clinical models however has hampered functional studies CAF heterogeneity. We demonstrate that our newly-generated biobank contains three FAP + -fibroblast subtypes, each unique molecular traits. Cultures an early-activated phenotype expressed the highest levels AR exhibited AR-dependent growth. Consistently, cells expressing early-activation markers co-expressed nuclear clinical specimens were enriched pre-neoplastic lesions/low-grade PCa. Conversely, myofibroblastic (myCAF), which low vitro vivo proliferatively-insensitive signaling modulation, constituted predominant subpopulation stromogenic high-grade PCa castration-resistant LACP9 patient-derived xenografts. Exacerbation myCAF state upon castration LAPC9-bearing hosts underscored these findings. Mechanistically, was driven by NFκB-TGFβ1-YAP1 axis, whose combined targeting synergistically repressed hallmarks impaired autophagic flux, effects potentiated enzalutamide resulting cell death. Collectively, findings provide mechanistic rationale for adjuvant YAP1-TGFβ axis improve patient outcomes.

Language: Английский

Citations

0
Analysis of Divergent Gene Expression between HPV+ and HPV- Head and Neck Squamous Cell Carcinoma Patients DOI Creative Commons
Kasturika Shankar, Sarah E. Walker

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract Human Papillomavirus (HPV) is a non-enveloped virus with circular double-stranded DNA genome. It one of the most common sexually transmitted infections, high-risk types such as HPV-16 and HPV-18 linked to anogenital head neck squamous cell carcinomas (HNSCC). HNSCC includes cancers oral cavity, pharynx, larynx, related regions, caused by carcinogens or persistent viral infections. HPV-positive (HPV+) cases are more prevalent in Western countries exhibit better prognosis treatment response compared HPV-negative (HPV-) cases. These differences suggest distinct fundamental between each subtype. This study analyzed RNA-seq data from PanCancer Atlas 2018 dataset investigate molecular distinctions HPV+ HPV-HNSCC. Using dimensionality reduction techniques Principal Component Analysis (PCA) Uniform Manifold Approximation Projection (UMAP), clear clustering was observed, suggesting unique gene expression profile. tumors exhibited upregulation genes involved nucleic acid processing downregulation associated apoptosis epidermis development. findings underscore biological HPV-HNSCC, offering insights into HPV-driven oncogenesis. Understanding these may improve patient stratification inform targeted therapeutic strategies for HNSCC.

Language: Английский

Citations

0