The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2− Breast Cancer
1
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 2360004, Japan
3
Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan
4
Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
5
Department of Surgery, Holy Cross Hospital, Michael and Dianne Bienes Comprehensive Cancer Center, Fort Lauderdale, FL 33308, USA
6
Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
7
Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518520, Japan
8
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 9601295, Japan
9
Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
10
Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518510, Japan
11
Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 1608402, Japan
*
Author to whom correspondence should be addressed.
Cells 2020, 9(7), 1643; https://doi.org/10.3390/cells9071643
Received: 22 May 2020
/
Revised: 28 June 2020
/
Accepted: 7 July 2020
/
Published: 8 July 2020
(This article belongs to the Special Issue Cell Cycle Control and Cancer)
E2F transcription factors play critical roles in the cell cycle. Therefore, their activity is expected to reflect tumor aggressiveness and responsiveness to therapy. We scored 3905 tumors of nine breast cancer cohorts for this activity based on their gene expression for the Hallmark E2F targets gene set. As expected, tumors with a high score had an increased expression of cell proliferation-related genes. A high score was significantly associated with shorter patient survival, greater MKI67 expression, histological grade, stage, and genomic aberrations. Furthermore, metastatic tumors had higher E2F scores than the primary tumors from which they arose. Although tumors with a high score had greater infiltration by both pro- and anti-cancerous immune cells, they had an increased expression of immune checkpoint genes. Estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative cancer with a high E2F score achieved a significantly higher pathological complete response (pCR) rate to neoadjuvant chemotherapy. The E2F score was significantly associated with the expression of cyclin-dependent kinase (CDK)-related genes and strongly correlated with sensitivity to CDK inhibition in cell lines. In conclusion, the E2F score is a marker of breast cancer aggressiveness and predicts the responsiveness of ER-positive/HER2-negative patients to neoadjuvant chemotherapy and possibly to CDK and immune checkpoint inhibitors.
View Full-Text
Keywords:
biomarker; breast cancer; cell cycle; cyclin-dependent kinase; E2F; gene set; GSVA; hormone receptor; immune checkpoint; metastasis; signaling pathway; treatment response
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 195 KiB)
MDPI and ACS Style
Oshi, M.; Takahashi, H.; Tokumaru, Y.; Yan, L.; Rashid, O.M.; Nagahashi, M.; Matsuyama, R.; Endo, I.; Takabe, K. The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2− Breast Cancer. Cells 2020, 9, 1643. https://doi.org/10.3390/cells9071643
AMA Style
Oshi M, Takahashi H, Tokumaru Y, Yan L, Rashid OM, Nagahashi M, Matsuyama R, Endo I, Takabe K. The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2− Breast Cancer. Cells. 2020; 9(7):1643. https://doi.org/10.3390/cells9071643
Chicago/Turabian StyleOshi, Masanori, Hideo Takahashi, Yoshihisa Tokumaru, Li Yan, Omar M. Rashid, Masayuki Nagahashi, Ryusei Matsuyama, Itaru Endo, and Kazuaki Takabe. 2020. "The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2− Breast Cancer" Cells 9, no. 7: 1643. https://doi.org/10.3390/cells9071643
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
