Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets
Recommended Citation
Kołodziejczak-Guglas I, Simões RLS, de Souza Santos E, Demicco EG, Lazcano Segura RN, Ma W, Wang P, Geffen Y, Storrs E, Petralia F, Colaprico A, da Veiga Leprevost F, Pugliese P, Ceccarelli M, Noushmehr H, Nesvizhskii AI, Kamińska B, Priebe W, Lubiński J, Zhang B, Lazar AJ, Kurzawa P, Mesri M, Robles AI, Ding L, Malta TM, and Wiznerowicz M. Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets. Cell Genom 2025;5(6):100851.
Document Type
Article
Publication Date
6-11-2025
Publication Title
Cell Genom
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.
Medical Subject Headings
Humans; Proteomics; Neoplastic Stem Cells; Neoplasms; Cell Dedifferentiation; Protein Processing, Post-Translational; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor
PubMed ID
40250426
ePublication
ePub ahead of print
Volume
5
Issue
6
First Page
100851
Last Page
100851
