Study · Endometrial regulons

Robustness and cross-cohort concordance of developmental regulons in endometrial carcinoma

Prespecified TCGA-UCEC discovery with CPTAC-UCEC external evaluation, target-deletion robustness and clinical sensitivity analyses.

Authors

Draga Toncheva1Vasil Sgurev2Vladimir Mitev3

  1. 1Department of Biological Sciences, Bulgarian Academy of Sciences
  2. 2Institute of Information and Communication Technologies, Bulgarian Academy of Sciences
  3. 3Helena Bioinformatics EOOD

Abstract

This study asks whether the molecular classes of endometrial carcinoma differ in developmental regulatory programmes while keeping association, target-set robustness and cross-cohort transportability as separate claims.

A fetal Müllerian epithelial module and 20 prespecified developmental transcription-factor regulons were evaluated in TCGA-UCEC. Six signals then underwent external evaluation in two independent CPTAC-UCEC strata, together with deletion, purity, molecular-subtype, grade and histology sensitivity analyses.

Read the preprintView on GitHub

Two regulons hold their prespecified direction in an independent cohort. None is presented as a validated biomarker.

01 · Effect estimates

Cross-cohort forest plot

−1.5−1.0−0.50.0+0.5+1.0+1.5GATA2C2GATA2: d −0.553, 95% CI −0.855 to −0.287, q 0.0020−0.553SOX9C2SOX9: d −0.527, 95% CI −0.805 to −0.287, q 0.0020−0.527HOXA9C2HOXA9: d −0.646, 95% CI −0.921 to −0.382, q 0.0020−0.646WT1C2WT1: d −0.591, 95% CI −0.878 to −0.349, q 0.0020−0.591PAX8C1PAX8: d +0.693, 95% CI +0.473 to +0.924, q 0.0020+0.693LHX1C1LHX1: d +0.962, 95% CI +0.734 to +1.207, q 0.0020+0.962standardized effect size d
ZeroLocked |d| = 0.50 floorValues and intervals: GitHub scientific release
This site presents cohort-level research results. It does not provide patient-specific interpretation, treatment prediction or clinical decision support.
Releasev1.0.1
DiscoveryTCGA-UCEC · n=507
External evaluationCPTAC-UCEC · n=230
Scientific commitf702249bd50d

Six canonical targets

No ranking or composite score is used. Every verdict is derived from the pinned GitHub result tables.

02 · Separated evidence dimensions

Evidence map

Association, target-set robustness and transportability remain separate. No composite score is calculated.

TargetAssociationRobustnessTransportability
GATA2C2 Meets locked criteriaCAT2 DEPLETION No universal creditNo universal deletion credit Direction supportedExternally replicated direction
TCGA primaryd −0.553 · 95% CI −0.855 to −0.287 · q 0.0020
TCGA no purityd −0.539 · 95% CI −0.842 to −0.284
CPTAC Discoveryd −0.689 · 95% CI −1.409 to −0.045
CPTAC Confirmatoryd −0.999 · 95% CI −1.616 to −0.497
CPTAC metad −0.877 · 95% CI −1.306 to −0.449 · q 3.62e-4
Deletion ledger1/75 primary failures · worst NFE2
SOX9C2 Meets locked criteriaCAT2 DEPLETION No universal creditNo universal deletion credit Direction supportedExternally replicated direction
TCGA primaryd −0.527 · 95% CI −0.805 to −0.287 · q 0.0020
TCGA no purityd −0.509 · 95% CI −0.775 to −0.260
CPTAC Discoveryd −0.993 · 95% CI −1.735 to −0.264
CPTAC Confirmatoryd −0.641 · 95% CI −1.322 to −0.050
CPTAC metad −0.789 · 95% CI −1.254 to −0.323 · q 0.0018
Deletion ledger15/70 primary failures · worst XPO4
HOXA9C2 Meets locked criteriaCAT2 DEPLETION No universal creditNo universal deletion credit Unresolved / underpoweredevaluable: not replicated
TCGA primaryd −0.646 · 95% CI −0.921 to −0.382 · q 0.0020
TCGA no purityd −0.614 · 95% CI −0.894 to −0.354
CPTAC Discoveryd −0.550 · 95% CI −1.255 to +0.204
CPTAC Confirmatoryd −0.195 · 95% CI −0.797 to +0.377
CPTAC metad −0.333 · 95% CI −0.789 to +0.123 · q 0.1831
Deletion ledger2/19 primary failures · worst MYCN
WT1C2 Meets locked criteriaCAT2 DEPLETION No universal creditNo universal deletion credit Unresolved / underpoweredevaluable: not replicated
TCGA primaryd −0.591 · 95% CI −0.878 to −0.349 · q 0.0020
TCGA no purityd −0.598 · 95% CI −0.861 to −0.333
CPTAC Discoveryd −0.255 · 95% CI −0.794 to +0.390
CPTAC Confirmatoryd −0.115 · 95% CI −0.604 to +0.369
CPTAC metad −0.175 · 95% CI −0.547 to +0.198 · q 0.3584
Deletion ledger1/92 primary failures · worst SULF2
PAX8C1 Meets locked criteriaCAT1 ENRICHMENT Meets locked criteriaUniversal deletion credit Unresolved / underpoweredunderpowered sensitivity
TCGA primaryd +0.693 · 95% CI +0.473 to +0.924 · q 0.0020
TCGA no purityd +0.686 · 95% CI +0.471 to +0.925
CPTAC Discoveryd +0.500 · 95% CI −0.102 to +1.140
CPTAC Confirmatoryd +1.054 · 95% CI +0.508 to +1.649
CPTAC metad +0.795 · 95% CI +0.379 to +1.212 · q 5.54e-4
Deletion ledger0/23 primary failures · worst SLC3A1
LHX1C1 Meets locked criteriaCAT1 ENRICHMENT Meets locked criteriaUniversal deletion credit Blocked by vetoOpposite-direction veto
TCGA primaryd +0.962 · 95% CI +0.734 to +1.207 · q 0.0020
TCGA no purityd +0.956 · 95% CI +0.725 to +1.217
CPTAC Discoveryd −0.031 · 95% CI −0.698 to +0.656
CPTAC Confirmatoryd +1.048 · 95% CI +0.396 to +1.834
CPTAC metad +0.470 · 95% CI −0.013 to +0.953 · q 0.0845
Deletion ledger0/6 primary failures · worst HHEX