Figure 5.

High ZMIZ1 expression correlates with low survival in ER-positive patients, ZMIZ1 and ER transcriptional activities correlate in patient samples, and ZMIZ1 and ER are co-localised in patient samples. (A) Stratifying patients of ER-positive (left) breast cancer based on ZMIZ1 expression shows that high levels of ZMIZ1 results in a significant reduction in patient survival. The effect is not seen with ER-negative (right) breast cancer, implying an ER-positive specific function for ZMIZ1 in breast cancer. (B) Stratifying ER-positive breast cancer based on treatment, either no endocrine therapy or tamoxifen only, shows that high levels of ZMIZ1 results in a significant reduction in patient survival for patients who receive tamoxifen. The effect is not seen for the ‘no endocrine therapy’ patients (left), further supporting an interaction between ZMIZ1 with the ER signalling pathway in breast cancer. (C) Transcriptional activity of ESR1 and ZMIZ1, as measured by the VIPER algorithm, correlate in both the METABRIC and TCGA cohort, thus confirming both transcription factors are transcriptionally active within ER-positive tumours and potentially function together in ER-positive tumours. (D) Consecutive slides derived from biopsy samples of three patients with ER-positive breast cancer were stained by IHC for both the estrogen receptor-α and ZMIZ1. In all three patients, the localisation of staining for the proteins was specific to the tumour cells and the nucleus. In contrast, the stromal cells show little or no expression of either protein. Scale: 50 µm. (E) Correlation of protein abundance for ZMIZ1, ER and KI67 in breast cancer tumours in the TCGA cohort (from PXD024322). ZMIZ1 correlates significantly with KI67 protein expression, a marker of proliferation.