High Intratumoral PROS1 Expression Is Associated with Improved Survival, Reduced Hypoxia Score Markers, and Alterations in Gene Expression Associated with Oncogene Signaling and Cell Cycle Signaling in Selected Solid Tumors
- 1Department of Interdisciplinary Oncology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
- 2Department of Microbiology, Genetics & Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Abstract
Protein S (PS), encoded by PROS1, is a vitamin K-dependent physiological anticoagulant with emerging, context-dependent roles in tumor biology. In pancreatic ductal adenocarcinoma (PDAC), exogenous PS suppresses tumor growth and intratumoral hypoxia in preclinical models. Notably, high intratumoral PROS1 expression is associated with improved survival and attenuation of oncogenic, hypoxia-responsive, and EMT-related transcriptional programs in PDAC. Here, we examined associations between intratumoral PROS1 expression and overall survival, hypoxia-associated signaling, and genomic instability across nine cancer types using publicly available cBioPortal datasets. Tumors were stratified by low versus high PROS1 expression. Genomic instability was assessed using tumor mutational burden, aneuploidy, and tumor break load, where available. High PROS1 expression was associated with improved survival in ovarian serous cystadenocarcinoma and lung adenocarcinoma in exploratory, unadjusted Mantel-Haenszel hazard ratio analyses. It was also inversely associated with genomic instability markers in ovarian, lung adenocarcinoma, and PDAC. Meta-analyses in select genes under low and high PROS1 expression conditions revealed shifts in pathways linked to oncogenic signaling, cell-cycle regulation, hypoxia, and EMT. Collectively, these findings position PROS1 as a candidate prognostic biomarker in selected cancers and support further investigation of PROS1’s roles in limiting tumor progression and preserving genomic stability.
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BibTeX
@article{prouse2026high,
title = {{High Intratumoral PROS1 Expression Is Associated with Improved Survival, Reduced Hypoxia Score Markers, and Alterations in Gene Expression Associated with Oncogene Signaling and Cell Cycle Signaling in Selected Solid Tumors}},
author = {Teagan Prouse and Rinku Majumder and Samarpan Majumder},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219613},
url = {https://www.mdpi.com/1422-0067/27/21/9613},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High Intratumoral PROS1 Expression Is Associated with Improved Survival, Reduced Hypoxia Score Markers, and Alterations in Gene Expression Associated with Oncogene Signaling and Cell Cycle Signaling in Selected Solid Tumors
AU - Teagan Prouse
AU - Rinku Majumder
AU - Samarpan Majumder
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219613
UR - https://www.mdpi.com/1422-0067/27/21/9613
AB - Protein S (PS), encoded by PROS1, is a vitamin K-dependent physiological anticoagulant with emerging, context-dependent roles in tumor biology. In pancreatic ductal adenocarcinoma (PDAC), exogenous PS suppresses tumor growth and intratumoral hypoxia in preclinical models. Notably, high intratumoral PROS1 expression is associated with improved survival and attenuation of oncogenic, hypoxia-responsive, and EMT-related transcriptional programs in PDAC. Here, we examined associations between intratumoral PROS1 expression and overall survival, hypoxia-associated signaling, and genomic instability across nine cancer types using publicly available cBioPortal datasets. Tumors were stratified by low versus high PROS1 expression. Genomic instability was assessed using tumor mutational burden, aneuploidy, and tumor break load, where available. High PROS1 expression was associated with improved survival in ovarian serous cystadenocarcinoma and lung adenocarcinoma in exploratory, unadjusted Mantel-Haenszel hazard ratio analyses. It was also inversely associated with genomic instability markers in ovarian, lung adenocarcinoma, and PDAC. Meta-analyses in select genes under low and high PROS1 expression conditions revealed shifts in pathways linked to oncogenic signaling, cell-cycle regulation, hypoxia, and EMT. Collectively, these findings position PROS1 as a candidate prognostic biomarker in selected cancers and support further investigation of PROS1’s roles in limiting tumor progression and preserving genomic stability.
SN - 1422-0067
ER -