Journal: medRxiv
Article Title: THR-6E: A Six-Gene Cell-of-Origin Signature Stratifies Risk and Predicts Systemic Therapy Response in ER+/HER2− Breast Cancer
doi: 10.64898/2026.01.31.26345244
Figure Lengend Snippet: (a) THR-6E and MKI67 (Ki67) expression across normal breast glandular epithelial cell subsets in the Human Protein Atlas (HPA) single-cell RNA-seq dataset (v23). Values are reported as normalized transcripts per million (nTPM) for the indicated epithelial clusters (C1, C4, C9, C11, C16, C17, C21). (b) Fraction of cells expressing ESR1 (ER), AR, and VDR across the same glandular breast epithelial clusters in HPA (v23). Percent expression denotes the proportion of cells within each cluster with detectable transcript. (c) Gene–gene correlation matrices for THR-6E and PAM50 gene sets in normal breast tissue (top) and breast tumors (bottom) from TNMplot. Colors represent Spearman correlation coefficients (−1 to 1). (d) Genomic alteration frequencies for THR-6E, Oncotype DX, and PAM-50 gene sets in breast cancer using combined TCGA-BRCA and METABRIC cohorts (total n=3,593). Alterations include mutations and copy-number changes as reported by cBioPortal. THR-6E genes show low alteration frequency (mean 1.1%), whereas Oncotype DX and PAM-50 include multiple genes with recurrent copy-number gains (15–20% in queried genes). (e) Protein–protein interaction network of THR-6E with ESR1, AR, and VDR generated using STRING (v12.0) with k-means clustering. Orange arrows indicate literature-supported regulatory relationships overlaid on the STRING network. (f) CancerGeneNet (SIGNOR) network linking THR-6E genes to cancer-associated phenotypes. Query proteins are shown in yellow, first neighbors in green; protein families are shown as white circles and protein complexes as blue clover symbols. Solid edges denote direct interactions and dashed edges denote indirect interactions; blue arrows indicate up-regulation and red T-bars indicate down-regulation.
Article Snippet: THR-6E expression in normal tissues is breast-enriched and maps to specific glandular epithelial cell subsets. (a) Tissue-level expression of ESR1 (ER), AR, and VDR and the six THR-6E gene products (KIF4A, KIF2C, CDC20, FAM64A/PIMREG, TPX2, and LMNB2) across normal human tissues, queried in ProteomicsDB. (b) Cluster-level expression of THR-6E, ESR1 (ER), AR, VDR, and MKI67 (Ki67) across normal human breast glandular epithelial cell clusters (C1, C4, C9, C11, C16, C17, C20, C21) from the Human Protein Atlas (HPA) single-cell dataset (v23).
Techniques: Expressing, Single Cell, RNA Sequencing, Generated