Maiti Aparna, Okano Ichiro, Oshi Masanori, Okano Maiko, Tian Wanqing, Kawaguchi Tsutomu, Katsuta Eriko, Takabe Kazuaki, Yan Li, Patnaik Santosh, Hait Nitai C
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Molecular & Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancers (Basel). 2021 May 27;13(11):2641. doi: 10.3390/cancers13112641.
Heterogeneity is the characteristic of breast tumors, making it difficult to understand the molecular mechanism. Alteration of gene expression in the primary tumor versus the metastatic lesion remains challenging for getting any specific targeted therapy. To better understand how gene expression profile changes during metastasis, we compare the primary tumor and distant metastatic tumor gene expression using primary breast tumors compared with its metastatic variant in animal models. Our RNA sequencing data from cells revealed that parental cell and the metastatic variant cell are different in gene expression while gene signature significantly altered during metastasis to distant organs than primary breast tumors. We found that secreted mediators encoding genes (ANGPTL7, MMP3, LCN2, S100A8, and ESM1) are correlated with poor prognosis in the clinical setting as divulged from METABRIC and TCGA-BRCA cohort data analysis.
异质性是乳腺肿瘤的特征，这使得理解其分子机制变得困难。原发性肿瘤与转移病灶中基因表达的改变对于获得任何特异性靶向治疗仍然具有挑战性。为了更好地理解转移过程中基因表达谱是如何变化的，我们在动物模型中，将原发性乳腺肿瘤与其转移变体进行比较，以对比原发性肿瘤和远处转移肿瘤的基因表达。我们从细胞获得的RNA测序数据显示，亲代细胞和转移变体细胞在基因表达上存在差异，并且与原发性乳腺肿瘤相比，在转移至远处器官的过程中基因特征发生了显著改变。我们发现，从METABRIC和TCGA - BRCA队列数据分析中可知，分泌介质编码基因（ANGPTL7、MMP3、LCN2、S100A8和ESM1）与临床环境中的不良预后相关。
