Abstract
The clinical benefits of the MammaPrint® signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint® signature genes are perturbated to a specific phase of the cell cycle. The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells.
Highlights
Breast cancer remains one of the most devastating diseases worldwide
The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells
We obtained single-cell transcriptomes from these Fucci cells with our microfluidic platform with nanoliter reactors [5]
Summary
Breast cancer remains one of the most devastating diseases worldwide. Traditionally, estrogen receptor (ER), progesterone receptor (PR) and Her have been used to classify breast cancer into three subtypes: positive for hormonal receptors (ER+), Her2+, and triple negative (TNBC) without these receptors. Based on the 70-gene MammaPrint® signature, the same group reported a follow-up NEJM article, showing that “no chemotherapy led to a 5-year rate of survival without distant metastasis that was 1.5% lower than the rate with chemotherapy”, with 1550 patients (23.2%) at high clinical risk and low genomic risk for recurrence, out of a randomized Phase 3 study with 6693 enrolled early-stage breast cancer patients [3]. This suggests that approximately 46% of women at high clinical risk may not need chemotherapy. It is not clear why these genes have predictive power and whether such a panel can be applied to other types of cancers
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