Faculty, Staff and Student Publications

Publication Date

6-11-2025

Journal

Cell Genomics

DOI

10.1016/j.xgen.2025.100851

PMID

40250426

PMCID

PMC12230239

PubMedCentral® Posted Date

4-17-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Cancer progression and therapeutic resistance are closely linked to a stemness phenotype. Here, we introduce a protein-expression-based stemness index (PROTsi) to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes. Utilizing datasets from the Clinical Proteomic Tumor Analysis Consortium across 11 tumor types, we validate PROTsi's effectiveness in accurately quantifying stem-like features. Through integration of PROTsi with multi-omics, including protein post-translational modifications, we identify molecular features associated with stemness and proteins that act as active nodes within transcriptional networks, driving tumor aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets, both shared and tumor specific. These stemness-associated proteins demonstrate predictive value for clinical outcomes, as confirmed by immunohistochemistry in multiple samples. The findings emphasize PROTsi's efficacy as a valuable tool for selecting predictive protein targets, a crucial step in customizing anti-cancer therapy and advancing the clinical development of cures for cancer patients.

Keywords

Humans, Proteomics, Neoplastic Stem Cells, Neoplasms, Cell Dedifferentiation, Protein Processing, Post-Translational, Gene Expression Regulation, Neoplastic, Biomarkers, Tumor

Published Open-Access

yes

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