J Cancer 2020; 11(21):6326-6336. doi:10.7150/jca.46466

Research Paper

O-6-methylguanine DNA methyltransferase is a favorable biomarker with proliferation suppressive potential in Breast Cancer

Danxia Lin1,2*, Yingsheng Xiao3*, Binliang Huang4, Xiao Wu5, Chunfa Chen2,6, Yuanke Liang7, De Zeng1,2✉

1. Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou 515031, PR China.
2. Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, No. 7 Raoping Road, Shantou 515031, PR China.
3. Department of Thyroid Surgery, Shantou Central Hospital, No. 114 Waima Road, Shantou 515031, PR China.
4. Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou, PR China.
5. Cancer Research Center, Shantou University Medical College, No. 22 Xinlin Road, Shantou 515031, PR China.
6. The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, PR China.
7. Department of Thyroid and Breast Surgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China.
*These authors contributed equally to this work.

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Citation:
Lin D, Xiao Y, Huang B, Wu X, Chen C, Liang Y, Zeng D. O-6-methylguanine DNA methyltransferase is a favorable biomarker with proliferation suppressive potential in Breast Cancer. J Cancer 2020; 11(21):6326-6336. doi:10.7150/jca.46466. Available from http://www.jcancer.org/v11p6326.htm

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Abstract

Background: The O6-methylguanine-DNA methyltransferase (MGMT) is a highly effective enzyme capable of repairing DNA damage to maintain genomic stability. Until recently, reports on the expression and potential role of MGMT in breast cancer remain controversial. This study is intended to elucidate the prognostic significance and potential function of MGMT in breast cancer.

Materials and methods: The immunohistochemistry assay and a series of public databases were utilized to determine the relevance between MGMT expression and clinicopathological characteristics, as well as survival outcomes in patients with breast cancer. The western blotting, qRT-PCR, proliferation, colony formation and transwell assays were used to investigate the potential function of MGMT in breast cancer cells.

Results: The immunohistochemistry analysis and public cancer databases exploration demonstrated that MGMT expression was significantly related to estrogen receptor (ER) positivity in breast cancer. Positive expression of MGMT predicts a longer distant-free survival (DFS) and overall survival (OS) in patients with breast cancer, especially in ER-positive tumor. The mRNA level of MGMT was significantly associated with those of ESR1, GATA3 and FOXA1 in ER-positive breast tumor. Down-regulation of MGMT expression enhanced the proliferative and invasive capacities of breast cancer cells through PTEN/AKT pathway.

Conclusions: MGMT is a favorable biomarker with proliferation suppressive potential in ER-positive breast cancer. Future study on targeted modulation of MGMT in the treatment of breast cancer is warranted.

Keywords: breast cancer, O6-methylguanine-DNA methyltransferase (MGMT), prognosis, immunohistochemistry (IHC), IRS, immunoreactive score