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Tytuł pozycji:

The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2- Breast Cancer.

Tytuł:
The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2- Breast Cancer.
Autorzy:
Oshi M; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.; Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 2360004, Japan.
Takahashi H; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Tokumaru Y; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.; Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.
Yan L; Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Rashid OM; Department of Surgery, Holy Cross Hospital, Michael and Dianne Bienes Comprehensive Cancer Center, Fort Lauderdale, FL 33308, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Nagahashi M; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518520, Japan.
Matsuyama R; Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 2360004, Japan.
Endo I; Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 2360004, Japan.
Takabe K; Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.; Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 2360004, Japan.; Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 9601295, Japan.; Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA.; Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 9518510, Japan.; Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 1608402, Japan.
Źródło:
Cells [Cells] 2020 Jul 08; Vol. 9 (7). Date of Electronic Publication: 2020 Jul 08.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI
MeSH Terms:
Biomarkers, Tumor/*metabolism
Breast Neoplasms/*metabolism
Breast Neoplasms/*pathology
E2F Transcription Factors/*metabolism
Receptor, ErbB-2/*metabolism
Receptors, Estrogen/*metabolism
Biomarkers, Tumor/genetics ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Disease-Free Survival ; E2F Transcription Factors/genetics ; Female ; Humans ; Receptor, ErbB-2/genetics ; Receptors, Estrogen/genetics
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Grant Information:
R01 CA160688 United States CA NCI NIH HHS; P30 CA016056 United States CA NCI NIH HHS
Contributed Indexing:
Keywords: E2F; GSVA; biomarker; breast cancer; cell cycle; cyclin-dependent kinase; gene set; hormone receptor; immune checkpoint; metastasis; signaling pathway; treatment response
Substance Nomenclature:
0 (Biomarkers, Tumor)
0 (Cell Cycle Proteins)
0 (E2F Transcription Factors)
0 (Receptors, Estrogen)
EC 2.7.10.1 (ERBB2 protein, human)
EC 2.7.10.1 (Receptor, ErbB-2)
Entry Date(s):
Date Created: 20200712 Date Completed: 20210412 Latest Revision: 20210412
Update Code:
20240105
PubMed Central ID:
PMC7407968
DOI:
10.3390/cells9071643
PMID:
32650578
Czasopismo naukowe
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.

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