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Article

G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer

1
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
3
Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, 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
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
8
Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14263, USA
9
Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
10
Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2921; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082921
Received: 31 March 2020 / Revised: 20 April 2020 / Accepted: 20 April 2020 / Published: 22 April 2020
(This article belongs to the Special Issue Metastasis Inhibition)
The vast majority of breast cancer death is a result of metastasis. Thus, accurate identification of patients who are likely to have metastasis is expected to improve survival. The G2M checkpoint plays a critical role in cell cycle. We hypothesized that breast cancer tumors with high activity of G2M pathway genes are more aggressive and likely to metastasize. To test this, we used the single-sample gene set variation analysis method to calculate the score for the Hallmark G2M checkpoint pathway using gene expression data of a total of 4626 samples from 12 human breast cancer cohorts. As expected, a high G2M pathway score correlated with enriched tumor expression of other cell proliferation-related gene sets. The score was significantly associated with clinical aggressive features of tumors and patient survival in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Interestingly, a high G2M score of metastasis tumors was also significantly associated with worse survival. In primary as well as metastasis tumors with high scores, the infiltration of both pro- and anti-cancerous immune cells increased. Tumor G2M score was also associated with treatment response to systemic chemotherapy in ER-positive/HER2-negative cancer, and was predictive of response to cyclin-dependent kinase inhibition therapy. View Full-Text
Keywords: breast cancer; biomarker; cell cycle; gene set; G2M; metastasis; pathway analysis; tumor gene expression breast cancer; biomarker; cell cycle; gene set; G2M; metastasis; pathway analysis; tumor gene expression
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MDPI and ACS Style

Oshi, M.; Takahashi, H.; Tokumaru, Y.; Yan, L.; Rashid, O.M.; Matsuyama, R.; Endo, I.; Takabe, K. G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer. Int. J. Mol. Sci. 2020, 21, 2921. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082921

AMA Style

Oshi M, Takahashi H, Tokumaru Y, Yan L, Rashid OM, Matsuyama R, Endo I, Takabe K. G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer. International Journal of Molecular Sciences. 2020; 21(8):2921. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082921

Chicago/Turabian Style

Oshi, Masanori, Hideo Takahashi, Yoshihisa Tokumaru, Li Yan, Omar M. Rashid, Ryusei Matsuyama, Itaru Endo, and Kazuaki Takabe. 2020. "G2M Cell Cycle Pathway Score as a Prognostic Biomarker of Metastasis in Estrogen Receptor (ER)-Positive Breast Cancer" International Journal of Molecular Sciences 21, no. 8: 2921. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082921

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