- - - Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
- - - Department of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- - - Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
- - - Iran National Tumor Bank, Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
- - - Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran

Background & Objective: This study examined the potential of human epididymis protein ۴ (HE۴) as a marker in early diagnosis or as a prognostic factor for breast cancer (BC) patients.Methods: A total of ۳۱ patients diagnosed with BC were enrolled in the study between ۲۰۰۸ and ۲۰۱۸. The mRNA and protein expression levels of HE۴ were analyzed by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR) in the BC tissue and the non-tumoral adjacent tissue. Using ELISA technique, HE۴ plasma levels were also measured in ۴۳ BC patients compared to ۴۳ healthy individuals. The correlation between HE۴ expression and clinicopathological features was then investigated.Results: An increase in HE۴ expression was observed at mRNA and protein levels in the BC group compared to the control group (p <۰.۰۱, p <۰.۰۰۰۱, respectively). In addition, the relative expression of HE۴ mRNA in BC patients showed a significant correlation with the differentiation grade of cancer cells (p <۰.۰۰۱). Plasma levels of HE۴ was also associated with grade (p <۰.۰۰۰۱), stage, and tumor size in BC patients (for both p <۰.۰۱). Patients with metastatic BC (p <۰.۰۱), lymphatic invasion, and lymph node involvement (for both p <۰.۰۵) showed significantly higher plasma levels of HE۴ expression than patients without metastasis.Conclusion: According to our findings, upregulation of HE۴ is probably related to invasive BC phenotype, and measuring plasma levels of HE۴ could be useful as a screening test in early diagnosis of BC.

Breast neoplasms, Gene expression, HE۴, WAP Four-Disulfide Core Domain Protein ۲, WFDC۲ Protein