Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
PLoS One. 2020 Mar 16;15(3):e0230261. doi: 10.1371/journal.pone.0230261. eCollection 2020.
We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA, and germline APOBEC3A/B deletion polymorphism in patients with breast cancers and to investigate the correlation between their expressions and clinicopathological characteristics.
RNA and DNA samples were extracted from 138 breast cancer tissues and adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using quantitative real-time polymerase chain reaction. Insertion and deletion PCR assays were performed to detect the A3B deletion allele. The serum concentrations of soluble programmed death-ligand 1 (sPD-L1) and interferon gamma were determined using enzyme-linked immunosorbent assays.
A3B mRNA expression levels were significantly higher in triple-negative breast cancers compared to hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers. Older age of the patient and high ki-67 expression were associated with increased expression levels of A3A and A3B mRNA. Advanced tumor stage, presence of lymph node involvement, and high histological grade were associated with increased expression levels of A3A mRNA. The APOBEC3A/B deletion allele was found in 77 (55.8%) patients. TP53 and PIK3CA mutations were detected in 62 (44.9%) and 31 (22.5%) patients, respectively. The presence of a PIK3CA mutation was associated with lower A3A mRNA expression levels. There was a weak positive relationship between A3A mRNA expression levels and serum sPD-L1 levels.
There was a difference in A3B mRNA expression levels according to breast cancer subtypes, and high levels of A3A and A3B mRNA expressions were associated with an aggressive phenotype. There was a high incidence of APOBEC3A/B deletion allele. Further studies are needed to identify the clinical significance of APOBEC in Asian patients with breast cancer.
本研究旨在评估 APOBEC3A（A3A）、3B（A3B）mRNA 表达及种系 APOBEC3A/B 缺失多态性在乳腺癌患者中的表达情况，并探讨其表达与临床病理特征的关系。
从 138 例乳腺癌组织和相应的癌旁正常组织中提取 RNA 和 DNA 样本。采用实时定量聚合酶链反应检测 A3A 和 A3B mRNA 转录本的水平。采用插入缺失聚合酶链反应检测 A3B 缺失等位基因。采用酶联免疫吸附试验检测可溶性程序性死亡配体 1（sPD-L1）和干扰素 γ的血清浓度。
与激素受体阳性、人表皮生长因子受体 2 阴性乳腺癌相比，三阴性乳腺癌中 A3B mRNA 表达水平显著升高。患者年龄较大和 ki-67 高表达与 A3A 和 A3B mRNA 表达水平升高有关。肿瘤分期较晚、淋巴结受累和组织学分级较高与 A3A mRNA 表达水平升高有关。在 77 例（55.8%）患者中发现 APOBEC3A/B 缺失等位基因。62 例（44.9%）和 31 例（22.5%）患者分别检测到 TP53 和 PIK3CA 突变。PIK3CA 突变与 A3A mRNA 表达水平降低有关。A3A mRNA 表达水平与血清 sPD-L1 水平呈弱正相关。
乳腺癌亚型间 A3B mRNA 表达水平存在差异，A3A 和 A3B mRNA 高表达与侵袭性表型相关。APOBEC3A/B 缺失等位基因发生率较高。需要进一步研究以确定 APOBEC 在亚洲乳腺癌患者中的临床意义。
