Gene expression profiles of breast cancer metastasis according to organ site

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry-based groups. Second, HER2-low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype-related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ-specific and subtype-independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions. 184 breast cancer metastasis在晚期乳腺癌中，通过转移性肿瘤活检开展生物标志物鉴定与患者筛选的需求愈发迫切。然而，针对不同器官转移部位的转移瘤生物学特征尚不明确。本研究对覆盖11种器官（包括肝、肺、脑与骨）的184份转移瘤样本中771个基因的表达情况进行了检测，并得到如下研究发现：其一，所有PAM50分子固有亚型（PAM50 molecular intrinsic subtypes）均在各器官转移瘤及免疫组化（immunohistochemistry）分组中存在分布；其二，HER2低表达（HER2-low）病灶在所有器官转移部位均被检出，包括骨转移灶，且HER2表达水平与ERBB2基因表达显著相关；其三，基因表达差异主要由分子固有亚型决定，而非转移器官部位；其四，分子亚型及各亚型相关基因/特征基因集均与总生存期显著相关；其五，本研究鉴定出74个具有器官特异性且与分子亚型无关的基因；最后，与脑转移或肝转移灶相比，肺转移灶的免疫特征表达水平更高。本研究结果表明，多种器官来源的转移瘤组织均可反映相关的肿瘤生物学特征；但同时也鉴定出了与转移器官部位相关的独特生物学特征，未来研究应探索其在诊断与治疗干预中的应用价值。184例乳腺癌转移样本