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Gene expression profile at single cell level of aortic cells from 2 adult R26-DreER;Ki67-CrexER;R26-GFP;Kdr rox/rox (Kdr-KO) mice after 8weeks of tamoxifen treatment.

ABSTRACT: The heterogeneity of endothelial cell proliferation is not addressed. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of aortic endothelial cell proliferation.

ORGANISM(S): Mus musculus

PROVIDER: GSE234386 | GEO | 2023/06/12

REPOSITORIES: GEO

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Project description:BackgroundControversy exists for the use of Ki67 protein expression as a predictive marker to select patients who do or do not derive benefit from adjuvant endocrine therapy. Whether other proliferation markers, like Cyclin D1, and mitotic count can also be used to identify those estrogen receptor α (ERα) positive breast cancer patients that derive benefit from tamoxifen is not well established. We tested the predictive value of these markers for tamoxifen benefit in ERα positive postmenopausal breast cancer patients.MethodsWe collected primary tumor blocks from 563 ERα positive patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial) with a median follow-up of 7.8 years. Mitotic count, Ki67 and Cyclin D1 protein expression were centrally assessed by immunohistochemistry on tissue microarrays. In addition, we tested the predictive value of CCND1 gene copy number variation using MLPA technology. Multivariate Cox proportional hazard models including interaction between marker and treatment were used to test the predictive value of these markers.ResultsPatients with high Ki67 (≥5%) as well as low (< 5%) expressing tumors equally benefitted from adjuvant tamoxifen (adjusted hazard ratio (HR) 0.5 for both groups)(p for interaction 0.97). We did not observe a significant interaction between either Cyclin D1 or Ki67 and tamoxifen, indicating that the relative benefit from tamoxifen was not dependent on the level of these markers. Patients with tumors with low mitotic count derived substantial benefit from tamoxifen (adjusted HR 0.24, p < 0.0001), while patients with tumors with high mitotic count derived no significant benefit (adjusted HR 0.64, p = 0.14) (p for interaction 0.03).ConclusionPostmenopausal breast cancer patients with high Ki67 counts do significantly benefit from adjuvant tamoxifen, while those with high mitotic count do not. Mitotic count is a better selection marker for reduced tamoxifen benefit than Ki67.

Dataset Information

Gene expression profile at single cell level of aortic cells from 2 adult R26-DreER;Ki67-CrexER;R26-GFP;Kdr rox/rox (Kdr-KO) mice after 8weeks of tamoxifen treatment.

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