IMR Press / FBL / Volume 28 / Issue 8 / DOI: 10.31083/j.fbl2808188
Open Access Original Research
MCM6 is a Poor Prognostic Biomarker and Promotes Progression in Breast Cancer
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1 Department of Pathology, Kunming Medical University, 650500 Kunming, Yunnan, China
2 Department of Pathology, First Affiliated Hospital of Kunming Medical University, 650032 Kunming, Yunnan, China
3 Department of General Surgery, Xinqiao Hospital, Army Medical University, 400037 Chongqing, China
*Correspondence: guoqing_pan@163.com (Guo-qing Pan)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(8), 188; https://doi.org/10.31083/j.fbl2808188
Submitted: 9 December 2022 | Revised: 11 March 2023 | Accepted: 15 March 2023 | Published: 30 August 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Breast cancer is the commonest global malignancy and the primary cause of carcinoma death. MCM6 is vital to carcinogenesis, but the pathogenesis of MCM6 remains unclear. Methods: MCM6 expression in patients with breast cancer was examined through The Cancer Genome Atlas (TCGA) database, immunohistochemistry, Quantitative Real-Time PCR (qRT‒PCR) and Western blotting. The prognostic factors were assessed by the Kaplan‒Meier method and Cox regression. On the basis of the key factors selected by multivariable Cox regression analysis, a nomogram risk prediction model was adopted for clinical risk assessment. The TCGA database was utilized to determine how MCM6 is correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, along with tumor mutation burden (TMB) and methylation. The impact of MCM6 on carcinoma cells was investigated in terms of proliferation, cell cycle as well as migrating and invasive behavior through CCK assays, flow cytometry, wound healing assays, Transwell assays and xenotransplantation experiments. Results: MCM6 expression was upregulated, which is closely associated with the size of the tumor (p = 0.001) and lymph node metastasis (p = 0.012) in patients with breast cancer. Multivariate analysis revealed MCM6 to be an independent risk factor for prognosis in patients with breast carcinoma. The nomograph prediction model included MCM6, age, ER, M and N stage, which displayed good discrimination with a C index of 0.817 and good calibration. Overexpression of MCM6 correlated with chemotherapy sensitivity, immune checkpoint-related genes (ICGs), tumor-infiltrating immune cells, tumor mutation burden (TMB), and methylation. Silencing MCM6 significantly inhibited proliferation, prolonged the G1 phase of the cell cycle, and restrained the proliferation, migration and invasive behavior of cancerous cells and inhibited tumor growth in vivo. Conclusions: Our research shows that MCM6 is highly expressed in breast cancer and can be used as an independent prognostic factor, which is expected to become a new target for the treatment of breast cancer in the future.

Keywords
breast cancer
MCM6
prognosis
nomogram
drug sensitivity
immune cell
Funding
82260512/National Natural Science Foundation of China
202201AS070076/Basic Research Program of Yunnan Province
202201AT070280/Basic Research Program of Yunnan Province
202101AY070001-016/Joint Projects of Applied Basic Research of Kunming Medical University and Yunnan Province Department of science and Technology
K1322121/Science and Technology Innovation team of Education Department of Yunnan Province
RLMY20200016/High-level personnel training program of Yunnan Province
Figures
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