Serum high-temperature-required protein A2: A potential biomarker for the diagnosis of breast cancer

Background: Breast cancer diagnosis is challenging because of the limited diagnostic efficiency of radiological measures and tumor markers such as carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA). Hence, diagnostic markers with acceptable accuracy are needed for breast cancer diagnosis. Objectives: This study was performed to assess the diagnostic power of circulating high-temperature-required protein A2 (HtrA2) mRNA expression in breast cancer detection and correlate its serum level with the clinicopathological characteristics of breast cancer patients. Methods: The HtrA2 mRNA expression was measured by reverse transcription-polymerase chain reaction (qRT-PCR) in the serum of 31 breast cancer patients and 28 healthy females. Results: The HtrA2 mRNA expression was significantly down-regulated in the serum of breast cancer patients compared to healthy controls (p < 0.001). Decreased HtrA2 expression was associated with poorly and moderately-differentiated tumor histological grade, distant metastasis, lymph node metastasis (N2), and TNM stages III and IV. The diagnostic power of HtrA2 was 0.868 with sensitivity and specificity of 77.4% and 85.7% respectively for the detection of breast cancer. Serum HtrA2 was negatively correlated with CA15-3 and CEA; this negative correlation revealed a significant relationship between these markers. The diagnostic power of combined HtrA2, CA15-3, and CEA was 0.947 with sensitivity and specificity of 83.9% and 96.4% respectively. Conclusions: HtrA2 is a potential serological diagnostic marker for breast cancer. HtrA2 is found to be correlated with poor histological grade, lymph node infiltration, distant metastasis, and advanced TNM stages. Combined detection of HtrA2 with CA15-3 and CEA could increase the diagnostic power of these markers.