Yi Shun, Zhou Wei
Department of Breast Surgery, The Affiliated Zhuzhou Hospital, Xiangya Medical College CSU Zhuzhou, Hunan, PR China.
Int J Clin Exp Pathol. 2020 Oct 1;13(10):2701-2709. eCollection 2020.
Breast cancer (BC) in adolescents and young adults (AYAs) accounts for 5.6% of BC in all women. BC in this population is often characterized as aggressive. Two-thirds of BC in AYAs belong to the hormone-receptor positive (HR(+))/human epidermal growth factor receptor 2 negative (HER2(-)) subtype. However, the underlying pathogenesis of this subtype has not been fully elucidated. To study HR(+)/HER2(-) BC in AYAs, we downloaded the available RNA-seq data from The Cancer Genome Atlas (TCGA) database and then performed differential expression gene screening and constructed a protein-protein interaction (PPI) network, identified the key genes, and did gene set enrichment analysis (GSEA). Based on the analyses, 32.26% of patients were in stage III. Additionally, we identified 1671 differentially expressed genes (DEGs) and 35 key genes. In addition, GSEA showed that ether lipid metabolism and complement and coagulation cascades were significantly enriched in the GNAI1 high expression phenotype. The key genes CXCL2, CXCL5, CXCL3, GPR37L1, NPY2R, OXGR1, NPW, CCL21, GNAI1, SAA1, GRM4, HCAR2, CX3CL1, GRM8, CCL28, SSTR1, PENK, P2RY12, NMUR1, NMU, ADCY5, TAS1R1, OXER1, GNG13, CCL16, CCR8, NPY5R, CXCL11, CXCL10, CXCL9, CXCL1, CXCL6, CCR4, and ANXA1 may be molecular markers of tumorigenesis of HR(+)/HER2(-) BC in AYAs. In addition, ether lipid metabolism and complement and coagulation cascades may be key pathways for GNAI1 regulation in HR(+)/HER2(-) BC in AYAs.
青少年及年轻成人（AYA）乳腺癌（BC）占所有女性乳腺癌的5.6%。该人群中的乳腺癌通常具有侵袭性。AYA乳腺癌的三分之二属于激素受体阳性（HR(+)）/人表皮生长因子受体2阴性（HER2(-)）亚型。然而，该亚型的潜在发病机制尚未完全阐明。为研究AYA中的HR(+)/HER2(-)乳腺癌，我们从癌症基因组图谱（TCGA）数据库下载了可用的RNA测序数据，然后进行差异表达基因筛选并构建蛋白质-蛋白质相互作用（PPI）网络，鉴定关键基因，并进行基因集富集分析（GSEA）。基于这些分析，32.26%的患者处于III期。此外，我们鉴定出1671个差异表达基因（DEG）和35个关键基因。此外，GSEA显示，醚脂代谢以及补体和凝血级联反应在GNAI1高表达表型中显著富集。关键基因CXCL2、CXCL5、CXCL3、GPR37L1、NPY2R、OXGR1、NPW、CCL21、GNAI1、SAA1、GRM4、HCAR2、CX3CL1、GRM8、CCL28、SSTR1、PENK、P2RY12、NMUR1、NMU、ADCY5、TAS1R1、OXER1、GNG13、CCL16、CCR8、NPY5R、CXCL11、CXCL10、CXCL9、CXCL1、CXCL6、CCR4和ANXA1可能是AYA中HR(+)/HER2(-)乳腺癌发生的分子标志物。此外，醚脂代谢以及补体和凝血级联反应可能是AYA中HR(+)/HER2(-)乳腺癌中GNAI1调控的关键途径。
