Identification of Genes Predicting Poor Response of Trastuzumab in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer.
Identification of Genes Predicting Poor Response of Trastuzumab in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer.
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DOI：
10.1155/2022/9529114
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发表时间：
2022
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
目的：研究人表皮生长因子受体2(HER2+)阳性乳腺癌患者的曲妥珠单抗耐药基因。从GEO(Gene Expression Omnibus)数据库中获取基因表达谱并进行分析。检测和评估曲妥珠单抗新辅助治疗队列中病理完全应答组和非病理完全应答组之间的差异表达基因，以及赫赛汀耐药细胞株和野生型细胞株之间的差异表达基因。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径分析筛选出具有功能的HUB基因。HUB基因的预后能力通过另一个曲妥珠单抗辅助治疗队列得到验证。通过分析两个与曲妥珠单抗耐药相关的GEO数据库，确定了50个上调的重叠DEG。功能分析筛选出10个线粒体功能和代谢途径丰富的HUB基因：ASCL1、CPT2、DLD、ELVOL7、GAMT、NQO1、SLC23A1、SPR、UQCRB和UQCRQ。这些HUB基因可以区分曲妥珠单抗耐药患者和敏感患者。HUB基因的进一步生存分析表明，在HER2+乳腺癌患者中，DLD过度表达与不良预后显著相关。目前已发现10个与曲妥珠单抗耐药相关的新基因，其中DLD可用于HER2+乳腺癌的曲妥珠单抗疗效预测和预后预测。
To identify trastuzumab-resistant genes predicting drug response and poor prognosis in human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Gene expression profiles from the GEO (Gene Expression Omnibus) database were obtained and analyzed. Differentially expressed genes (DEGs) between the pathological complete response (pCR) group and non-pCR group in a trastuzumab neoadjuvant therapy cohort and DEGs between Herceptin-resistant and wild-type cell lines were detected and evaluated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed to select the functional hub genes. The hub genes' prognostic power was validated by another trastuzumab adjuvant treatment cohort. Fifty upregulated overlapping DEGs were identified by analyzing two trastuzumab resistance-related GEO databases. Functional analysis picked out ten hub genes enriched in mitochondrial function and metabolism pathways: ASCL1, CPT2, DLD, ELVOL7, GAMT, NQO1, SLC23A1, SPR, UQCRB, and UQCRQ. These hub genes could distinguish patients with trastuzumab resistance from the sensitive ones. Further survival analysis of hub genes showed that DLD overexpression was significantly associated with an unfavorable prognosis in HER2+ breast cancer patients. Ten novel trastuzumab resistance-related genes were discovered, of which DLD could be used for trastuzumab response prediction and prognostic prediction in HER2+ breast cancer.
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影响因子：
4.6
作者：
Kahraman M;Röske A;Laufer T;Fehlmann T;Backes C;Kern F;Kohlhaas J;Schrörs H;Saiz A;Zabler C;Ludwig N;Fasching PA;Strick R;Rübner M;Beckmann MW;Meese E;Keller A;Schrauder MG
通讯作者：
Schrauder MG
影响因子：
64.5
作者：
DREBIN, JA;LINK, VC;GREENE, MI
通讯作者：
GREENE, MI
影响因子：
8
作者：
Han, Jing;Qu, Hongbo;Dong, Huaying
通讯作者：
Dong, Huaying
影响因子：
4.6
作者：
Wigner P;Zielinski K;Labieniec-Watala M;Marczak A;Szwed M
通讯作者：
Szwed M
影响因子：
3.5
作者：
Hong, YS;Kerr, DS;Patel, MS
通讯作者：
Patel, MS