01Case study 01
Case study 01
GNRHR expression across TNBC molecular subtypes

Does the LHRH/GnRH receptor (GNRHR), the target of an active TNBC nanoparticle-targeting strategy, express differently across TNBC's molecular subtypes? If it does, that would matter for how consistently a receptor-targeted therapy could work across the disease's biological variants.

116
TNBC patients
p = 0.71
Across subtypes
p = 0.98
Survival, log-rank

Result: no statistically significant difference across subtypes, and no relationship to survival in this cohort (TCGA), a real, well-caveated null result.

Single-cohort · Complete
02Case study 02
Case study 02
Systematic candidate screen, with cross-cohort validation

A gene-agnostic follow-up to Case Study 01: instead of testing one hand-picked gene, 15 candidates were sourced systematically from Open Targets' TNBC-associated target scores, then tested for subtype- and survival-association with Benjamini–Hochberg FDR correction applied across all 15 together, then scored on druggability (ChEMBL) and TNBC-specific literature coverage (PubMed).

15
Candidates screened
8 / 15
Significant after FDR
7 / 8
Replicated in METABRIC

The 8 FDR-significant genes were re-tested against METABRIC, a second, independent cohort (320 TNBC patients, nearly 3x the TCGA cohort) profiled on a different expression platform. 7 of 8 replicated on both. RRM2 did not (TCGA-significant, but p = 0.23 in METABRIC) and is reported as a miss, not dropped.

FTO is the standout candidate: significant in both cohorts, 91 potent ChEMBL ligands (a known druggable target), and only moderately studied in TNBC specifically (14 papers). Most other replicated genes (POLD1, POLD2, PRIM2, RRM1, TYMS, POLE) are DNA-replication-machinery genes, likely reflecting the known higher proliferation of the basal-like subtype rather than a subtype-specific mechanism on its own.

Status: computational only. Nothing here has been validated at the protein level yet, that's the next step, now underway with wet-lab flow cytometry.

Cross-cohort validated