Wu Jiayi, Zong Yu, Fei Xiaochun, Chen Xiaosong, Huang Ou, He Jianrong, Chen Weiguo, Li Yafen, Shen Kunwei, Zhu Li
Comprehensive Breast Health Center, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
Pathology Department, Shanghai Ruijin Hospital affiliated to Medical School of Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2014 Aug 25;9(8):e98673. doi: 10.1371/journal.pone.0098673. eCollection 2014.
The chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure.
In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines.
Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029-4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086-7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788-15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line.
Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer.
染色质结构域解旋酶/三磷酸腺苷酶DNA结合蛋白1样基因（CHD1L）是最近鉴定出的一种致癌基因，定位于1q21。原发性肝细胞癌中CHD1L蛋白的过表达与凋亡抑制增强、化疗敏感性降低和患者生存期缩短相关。然而，CHD1L蛋白状态或mRNA表达在乳腺癌中的情况及其临床意义仍不清楚。
在本研究中，对包含179例原发性浸润性乳腺癌和65例匹配的正常乳腺组织标本的组织芯片进行CHD1L表达的免疫组织化学染色。收集不同CHD1L状态的临床病理特征并进行比较。应用Kaplan-Meier曲线评估无病生存期（DFS）和总生存期（OS）。采用Cox回归分析确定独立的预后因素。此外，采用定量实时聚合酶链反应（QRT-PCR）评估CHD1L在6种乳腺癌细胞系中的mRNA水平表达。
179例患者中有87例（48.6%）存在CHD1L过表达，这与较年轻的年龄（P = 0.011）、更高的分级（P = 0.004）、更高的Ki-67指数（P = 0.018）和HER2过表达/扩增（P = 0.037）相关。中位随访55个月后，CHD1L过表达的患者DFS显著较差（82.6%对76.3%，P = 0.035），但OS无显著差异（87.0%对94.9%，P = 0.439）。多因素分析显示，CHD1L状态（HR = 2.169，[95%CI，1.029 - 4.573]，P = 0.042）、三阴性亚型（HR = 2.809，[95%CI 1.086 - 7.264]，P = 0.033）和HER2阳性亚型（HR = 5.221，[95%CI 1.788 - 15.240]，P =
