Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-0016, Japan.
Breast Cancer Res Treat. 2021 Apr;186(2):353-361. doi: 10.1007/s10549-020-06087-2. Epub 2021 Jan 18.
The homeobox (HOX) family consists of 39 genes whose expressions are tightly controlled and coordinated within the family, during development. We performed a comprehensive analysis of this gene family in cancer settings.
Gene correlation analysis was performed using breast cancer data available in The Cancer Genome Atlas (TCGA) and data from the patients admitted to our hospital. We also analyzed the data of normal breast tissue (GSE20437). We next collected gene expression and prognosis data of breast cancer patients (GSE11121, GSE7390, GSE3494, and GSE2990) and performed unsupervised hierarchal clustering by the HOX gene expression pattern and compared prognosis. We additionally performed this analysis to leukemia (available in TCGA) and sarcoma (GSE20196) data.
Gene correlation analysis showed that the proximal HOX genes exhibit strong interactions and are expressed together in breast cancer, similar to the expression observed during development. However, in normal breast tissue, less interactions were observed. Breast cancer microarray meta-data classified by the HOX gene expression pattern predicted the prognosis of luminal B breast cancer patients (p = 0.016). Leukemia (p = 0.00016) and sarcoma (p = 0.018) presented similar results. The Wnt signaling pathway, one of the major upstream signals of HOX genes in development, was activated in the poor prognostic group. Interestingly, poor prognostic cancer presented stronger correlation in the gene family compared to favorable prognostic cancer.
Comprehensive analysis of the HOX family demonstrated their similar roles in cancer and development, and indicated that the strong interaction of HOX genes might be specific to malignancies, especially in the case of poor prognostic cancer.
同源盒（HOX）家族由 39 个基因组成，其在发育过程中的表达受到严格的控制和协调。我们对癌症环境中的这个基因家族进行了全面分析。
使用癌症基因组图谱（TCGA）中提供的乳腺癌数据和我院患者的数据进行基因相关性分析。我们还分析了正常乳腺组织（GSE20437）的数据。接下来，我们收集了乳腺癌患者的基因表达和预后数据（GSE11121、GSE7390、GSE3494 和 GSE2990），并根据 HOX 基因表达模式进行无监督层次聚类，比较预后。我们还对白血病（TCGA 中可用）和肉瘤（GSE20196）数据进行了此分析。
基因相关性分析表明，近端 HOX 基因在乳腺癌中表现出强烈的相互作用并共同表达，这与发育过程中的表达相似。然而，在正常乳腺组织中，观察到的相互作用较少。根据 HOX 基因表达模式分类的乳腺癌微阵列元数据预测了 luminal B 型乳腺癌患者的预后（p=0.016）。白血病（p=0.00016）和肉瘤（p=0.018）也呈现出类似的结果。HOX 基因在发育过程中的主要上游信号之一 Wnt 信号通路在预后不良组中被激活。有趣的是，与预后良好的癌症相比，预后不良的癌症中基因家族的相关性更强。
对 HOX 家族的综合分析表明它们在癌症和发育中具有相似的作用，并表明 HOX 基因的强相互作用可能是恶性肿瘤特有的，尤其是在预后不良的癌症中。
