The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women

Jinyu Li; Xiajie Zhou; Lixi Li; Longtao Ji; Jiaqi Li; Yunhui Qu; Zhi Wang; Yutong Zhao; Jie Zhang; Feifei Liang; Jingjing Liu; Wanjian Gu; Rongxi Yang; Fei Ma; Liping Dai

doi:10.3389/fonc.2023.1148635

The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women

Front Oncol. 2023 May 18:13:1148635. doi: 10.3389/fonc.2023.1148635. eCollection 2023.

Authors

Jinyu Li¹, Xiajie Zhou², Lixi Li³, Longtao Ji^{4

5}, Jiaqi Li⁵, Yunhui Qu⁶, Zhi Wang^{4

5}, Yutong Zhao⁵, Jie Zhang⁷, Feifei Liang^{4

5}, Jingjing Liu⁵, Wanjian Gu⁷, Rongxi Yang², Fei Ma³, Liping Dai^{1

5}

Affiliations

¹ School of Basic Medical Sciences & The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
³ Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁴ BGI College, Zhengzhou University, Zhengzhou, Henan, China.
⁵ Henan Institute of Medical and Pharmaceutical Sciences & Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China.
⁶ Department of Clinical Laboratory in the First Affiliated Hospital & Key Clinical Laboratory of Henan Province, Zhengzhou University, Zhengzhou, Henan, China.
⁷ Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China.

Abstract

Purpose: Previous studies have shown that DNA methylation in peripheral blood may be associated with breast cancer (BC). To explore the association between the methylation level of the Cathepsin Z (CTSZ) gene in peripheral blood and BC, we conducted a case-control study in the Chinese population.

Methods: Peripheral blood samples were collected from 567 BC cases, 635 healthy controls, and 303 benign breast disease (BBD) cases. DNA extraction and bisulfite-specific PCR amplification were performed for all samples. The methylation levels of seven sites of the CTSZ gene were quantitatively determined by Mass spectrometry. The odds ratios (ORs) of CpG sites were evaluated for BC risk using per 10% reduction and quartiles analyses by logistic regression.

Results: Our analysis showed that five out of the seven CpG sites exhibited significant associations with hypomethylation of CTSZ and BC, compared to healthy controls. The highest OR was for Q2 of CTSZ_CpG_1 (OR: 1.62, P=0.006), particularly for early-stage breast cancer in the case of per 10% reduction of CTSZ_CpG_1 (OR: 1.20, P=0.003). We also found that per 10% reduction of CTSZ_CpG_5 (OR: 1.39, P=0.004) and CTSZ_CpG_7,8 (OR: 1.35, P=0.005) were associated with increased BC risk. Our study also revealed that four out of seven CpG sites were linked to increased BC risk in women under 50 years of age, compared to healthy controls. The highest OR was for per 10% reduction of CTSZ_CpG_1 (OR: 1.47, P<0.001). Additionally, we found that BC exhibited lower methylation levels than BBD at CTSZ_CpG_4 (OR for Q1: 2.18, P<0.001) and CTSZ_CpG_7,8 (OR for Q1: 2.01, P=0.001). Furthermore, we observed a correlation between methylation levels and tumor stage, ER, and HER2 status in BC patients.

Conclusion: Overall, our findings suggest that altered CTSZ methylation levels in peripheral blood may be associated with breast cancer, particularly in young women, and may serve as a potential biomarker for early-stage BC.

Keywords: CTSZ; Chinese women; DNA methylation; breast cancer; case-control study.