Genes
Integrative Multi-Omics and Single-Cell Analysis Prioritizes YWHAB Within Ubiquitination-Related Transcriptional Programs in Endometrial Carcinoma
Par Wang J, Zhu H, Li Y et 6 autres.
Contenu en anglais
Résumé
Background
Ubiquitination-related transcriptional programs may help characterize epithelial heterogeneity in endometrial carcinoma (EC). We aimed to identify candidates associated with these programs and epithelial plasticity.
Methods
We integrated a 43,613-cell atlas from five endometrioid EC samples and two normal endometrial samples with bulk transcriptomic, genetic-association and protein-expression data. Five scoring methods defined a consensus expression score, with HIGH and LOW quartiles defined within the Epithelial + EMT_like lineage. Differential expression and high-dimensional weighted gene co-expression network analysis (hdWGCNA) identified candidates for exploratory Mendelian randomization (MR) and survival-based prioritization among 541 patients from The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) cohort. Repeated nested cross-validation and cross-model feature support were used to evaluate internal performance and candidate stability. Pseudobulk, independently curated ubiquitin-proteasome system (UPS) gene sets and scSurv input masking provided sensitivity analyses.