Robustness and cross-cohort concordance of developmental regulons in endometrial carcinoma
Draga Toncheva, Vasil Sgurev, Vladimir Mitev
Submitted to npj Precision Oncology. The manuscript has not been peer reviewed.
- Published
- 2 August 2026
- Record type
- Preprint
- Version
- Version 1.0
- Article DOI
- 10.5281/zenodo.21763096
Abstract
Abstract
The analysis asks whether developmental regulon signals in endometrial carcinoma survive changes in target composition and retain their direction in an independent cohort. It keeps pointwise association, target-set robustness and cross-cohort transportability as separate claims.
Twenty prespecified developmental transcription-factor regulons and a fetal Mullerian epithelial module were evaluated in 507 TCGA-UCEC tumours. Six signals were then assessed in 230 CPTAC-UCEC tumours. The global fetal module was non-confirmatory.
GATA2 and SOX9 retained the same direction across cohorts but failed the universal single-target-deletion gate. HOXA9 and WT1 lacked external confirmation. PAX8 and LHX1 were internally robust but remained externally unresolved.
Evidence boundary
Evidence boundary
The results support directional concordance for selected regulons. They do not establish causal transcription-factor activity, biomarker validity, therapeutic dependence, treatment response or clinical utility. The preprint has not been peer reviewed.
01
Analysis design
TCGA-UCEC served as the discovery cohort. The analysis tested molecular-class associations and then removed individual targets to see whether a regulon-level result depended on one gene. CPTAC-UCEC provided an external check on the direction of six selected signals.
This sequence prevents an association from being described as robust or transportable before it passes the corresponding test.
02
Reproducibility record
The public repository contains the TCGA-UCEC discovery analysis, CPTAC-UCEC external evaluation, sensitivity analyses, provenance records, machine-readable results and release-verification tooling.
Repository concept DOI 10.5281/zenodo.21762178 identifies the computational record. Immutable release DOI 10.5281/zenodo.21762179 identifies version v1.0.1.