Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients.

Seri Jeong,Seho Park,Younhee Park,Hyon-Suk Kim,Oh-Joong Kwon,Byeong-Woo Park,Jianming Tang

doi:10.1371/journal.pone.0098284

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https://doi.org/10.1371/journal.pone.0098284

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Abstract

Human leukocyte antigen-G (HLA-G) is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G) was measured by enzyme-linked immunosorbent assay (ELISA) from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3′ untranslated region (UTR) 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407). Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL) compared to the control group (median 10.1 U/mL, P<0.001). The area under the receiver operating characteristic curve (AU-ROC) values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.

Highlights

Breast cancer is the most common cancer among women worldwide; approximately 1.2 million cases of breast cancer are diagnosed annually
2.Study subjects A total of 80 patients with breast cancer, who agreed to participate in our study, signed the informed consent form and received operations at our hospital, were randomly selected between July 2012 and July 2013
Characteristics of the study groups No significant difference was observed between the age of the subjects in all groups, according to the TNM stages, except between the control and overall breast cancer groups

Summary

Introduction

Breast cancer is the most common cancer among women worldwide; approximately 1.2 million cases of breast cancer are diagnosed annually. The overall incidence of breast cancer has increased, early diagnosis and treatment through screening have helped reduce the mortality from breast cancer [3]. The HLA-G gene encodes seven isoforms by alternative splicing of primary transcripts, which include four membrane-bound (HLA-G1, -G2, -G3, and -G4) and three soluble isoforms (HLA-G5, -G6, and -G7) [6]. Aberrant HLA-G expression has been closely associated with several pathological conditions, including transplantation, autoimmune and inflammatory diseases, viral infections, and malignancies [7]. The tolerogenic properties of HLA-G have beneficial effects in pregnancy, transplantation, and inflammatory diseases by reducing immune reaction responses, whereas they are deleterious in cancer and viral infections by permitting escape of tumor or virus-infected cells from anti-tumor or anti-viral responses, respectively [4]

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