CCDC12 gene methylation in peripheral blood as a potential biomarker for breast cancer detection

Abstract

Background

Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (CCDC12) implicated in tumorigenesis. This study aims to investigate the potential of blood-based CCDC12 methylation for breast cancer detection.

Methods

DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in CCDC12 gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between CCDC12 methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis.

Results

A total of eleven CpG sites were analyzed. The CCDC12 methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The CCDC12 methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER−/HER2+ breast cancer from the controls (AUC = 0.727).

Conclusion

The hypermethylation levels of CCDC12 in peripheral blood could be used for breast cancer detection.

CLINICAL SIGNIFICANCE

• Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers.

• The methylation levels of CpG sites in CCDC12 were higher in breast cancer than those in controls.

• The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls.

Keywords:

• CCDC12 methylation
• breast cancer detection
• biomarker

Authors’ Contributions

JJL analyzed the data and wrote the manuscript. YHQ, YTZ, FFL, LTJ, ZW and JYL performed material preparation and experiments. ZSZ, HXH, JZ and WJG performed the blood samples and clinical information collection. LPD and RXY contributed to the study design and revised the manuscript. All authors reviewed the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

The blood samples were collected upon the approval of the Ethics Committee of the First Affiliated Hospital of Zhengzhou University and the Jiangsu Province Hospital of Chinese Medicine (2021-KY-1058-002). All patients and healthy controls provided written informed agreement.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [Grant No. 82103629 and No. 81803303] and the Natural Science Foundation of Jiangsu Province [Grant No. BK20180674].