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

Leave-one-target-out robustness

Deletion results test dependence on individual regulon targets; they do not measure external replication.

03 · Gene leave-one-out

Deletion robustness map

Every mark is one mapped gene removed and re-estimated under the locked pointwise gate. Orange marks fall below |d| = 0.50.

GATA2

75 mapped genes
Failures
1/75
Minimum |d|
0.4950
Worst deletion
NFE2

SOX9

70 mapped genes
Failures
15/70
Minimum |d|
0.4593
Worst deletion
XPO4

HOXA9

19 mapped genes
Failures
2/19
Minimum |d|
0.4701
Worst deletion
MYCN

WT1

92 mapped genes
Failures
1/92
Minimum |d|
0.4877
Worst deletion
SULF2

PAX8

23 mapped genes
Failures
0/23
Minimum |d|
0.5767
Worst deletion
SLC3A1

LHX1

6 mapped genes
Failures
0/6
Minimum |d|
0.6999
Worst deletion
HHEX