Study on methylation sequence in the promoter region of the antigen presenting element (APM) gene in triple negative breast cancer

Xianglu Zhu^1,#, Shan Li^2,#, Gulizhareye·Aikula¹, Mukedaisi·Baiketiyaer¹, Youxi Han¹, Qian Cao1, Munire·Mushajiang^1,*

¹Department of Breast Radiotherapy, the Third Clinical Medical College (Affiliated Tumor Hospital), Xinjiang Medical University, Urumqi 830000, PR China - ²Department of Lymphoma, the Third Clinical Medical College (Affiliated Tumor Hospital), Xinjiang Medical University, Urumqi 830000, PR China

Objective: The methylation levels of HLA-I and APM elements in TNBC tissues were analyzed by Sequenom MassARRAY® DNA methylation mass spectrometry to identify the leading epigenetic modification in the occurrence of triple-negative breast cancer (TNBC).

Methods: For TAP1 and ERp57 genes, the MassARRAY methylation detection technique was used to quantitatively analyze the methylation level of the CpG island in the promoter region of the candidate gene, to identify the differences in the overall and single CpG methylation rate between TNBC and non-TNBC patients, as well as breast cancer tissues and breast fibroma tissues.

Results: The total methylation level of the ERp57 gene in TNBC tissues was significantly lower than that in non-TNBC tissues (P < 0.01), and there was no statistically significant difference in the total methylation level of the TAP1 gene between TNBC tissues and non-TNBC tissues (P > 0.05). The total methylation level of the ERp57 gene in breast cancer tissues was markedly lower than that in breast fibroma tissues (P < 0.05), and the total methylation level of the TAP1 gene was dramatically higher than that in breast fibroma tissues (P < 0.05). The methylation level of ER57-8-CpG-1, ER57-8-CpG-2.3.4, ER57-8-CpG-5, ER57-8-CpG-6.7, ER57-8-CpG-8, and ER57-8-CpG-9 sites in the promoter region of the ERp57 gene in TNBC tissues was remarkably lower than that in non-TNBC tissues (P < 0.01). The methylation level of ER57-8-CpG-1, ER57-8-CpG-2.3.4, ER57-8-CpG-5, ER57-8-CpG-8, and ER57-8-CpG-9 sites in the promoter region of the ERp57 gene in breast cancer tissues was significantly lower than that in breast fibroma tissues (P < 0.05). The methylation level of the TAP1-14-CpG-29 site in the promoter region of the TAP1 gene in breast cancer tissues was significantly higher than that in breast fibroma tissues (P < 0.05).

Conclusion: The methylation of the promoter region of APM member TAP1 and ERp57 genes plays an important role in the occurrence and development of TNBC.