An Integrated Model of the Transcriptome Landscape of HER2-Positive Breast Cancer. Homo sapiens

The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. Overall design: We analyzed RNA-seq data from a survey panel consisting of 8 benign breast lesions, 8 ER+, 8 triple negative, and 8 HER2-positive primary breast tumors to identify genomic features that were uniquely associated with HER2-positive tumors

本研究旨在构建针对HER2（Human Epidermal Growth Factor Receptor 2）阳性乳腺肿瘤的整合转录组图谱模型，并鉴定与HER2阳性肿瘤相关的关键信号通路。研究涉及的基因组特征包括三类：仅在HER2阳性肿瘤中差异表达的685个基因、仅在HER2阳性肿瘤中呈现独特可变剪接模式的102个基因，以及仅在HER2阳性肿瘤中携带特异性单核苷酸序列变异（eSNVs，expressed single nucleotide sequence variants）的303个基因。通过网络分析将上述基因组特征整合为转录组图谱模型，最终鉴定出12个高度相互关联的细胞过程，这些过程对HER2阳性肿瘤的建立与维持至关重要。研究观察到，整合素信号通路在体外与拉帕替尼（lapatinib）敏感性相关，且在NCCTG N9831辅助曲妥珠单抗临床试验数据集中与复发风险显著相关。总体设计：本研究分析了一组测序样本面板的RNA-seq（RNA Sequencing）数据，该面板包含8例良性乳腺病变、8例雌激素受体阳性（ER+）乳腺肿瘤、8例三阴性乳腺肿瘤以及8例HER2阳性原发性乳腺肿瘤，旨在鉴定仅与HER2阳性肿瘤特异性相关的基因组特征。