Differential expression of genes and protein networks in the primary breast tumor that proceed to distant metastasis. Homo sapiens

The presence or absence of lymph node metastasis plays a major role in the prediction of prognosis and subsequent patient management. However, good proportion of patients who display lymph node positivity remain disease free for 3 years or more, after the initial treatment, while a third of those who were lymph node negative at presentation, develop distant metastasis within the same period. We performed gene expression profiling on a cohort Indian breast cancer patients followed up for a period of 3-5 years and in comparison with a previously published Caucasian cohort data, we identified gene signatures that are associated with distant metastasis. This association was irrespective of the hormone receptor status. Our results show that the genes that signify immune system development and response are repressed, while factors for DNA replication are up regulated in patients who develop distant metastasis. A large number of genes encoding proteins involved in the mitotic spindle formation that belong to the TRIM28 protein network, are differentially regulated in the metastatic tumors. Also, there was a significant overlap of genes reported in a mouse model of bone metastasis, with patients who developed bone metastasis in our cohort. In conclusion, we present for the first time probable gene signatures that correlate with distant metastasis in breast cancer patients irrespective of nodal or hormone receptor status Overall design: 80 indian breast cancer patients(samples),comprising of 22ER+(estrogen receptor),and 55 ER-.PR(progesterone receptor) ,HER and NOD status are also given in corresponding sample title and array files

淋巴结转移（lymph node metastasis）的有无是预测患者预后及指导后续临床诊疗的核心因素。然而，相当比例的淋巴结阳性患者在接受初始治疗后可实现3年及以上的无病生存；而初诊时淋巴结阴性的患者中，有三分之一会在同期发生远处转移（distant metastasis）。本研究对一组随访时长3至5年的印度乳腺癌患者队列开展基因表达谱分析（gene expression profiling），并与已发表的高加索人群（Caucasian）队列数据进行对照，最终鉴定出与远处转移相关的基因特征（gene signatures）。该关联不受激素受体状态（hormone receptor status）的影响。研究结果显示，在发生远处转移的患者中，参与免疫系统发育与应答的基因表达被抑制，而与DNA复制（DNA replication）相关的因子表达则被上调。隶属于TRIM28蛋白网络（TRIM28 protein network）、参与有丝分裂纺锤体形成（mitotic spindle formation）的大量编码蛋白基因，在转移性肿瘤中呈现差异表达。此外，本队列中发生骨转移（bone metastasis）的患者，其差异表达基因与骨转移小鼠模型中报道的基因存在显著重叠。综上，本研究首次报道了与乳腺癌患者远处转移相关的潜在基因特征，且该特征不受淋巴结状态或激素受体状态的影响。
实验整体设计：本研究纳入80例印度乳腺癌患者（样本），其中22例为雌激素受体（estrogen receptor，ER）阳性（ER+）、55例为ER阴性；同时提供了孕激素受体（progesterone receptor，PR）、HER及淋巴结（NOD）状态信息，相关信息已标注于对应样本标题及基因芯片文件中。