Expression-Based Diagnosis, Treatment Selection, and Drug Development for Breast Cancer.
Expression-Based Diagnosis, Treatment Selection, and Drug Development for Breast Cancer.
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DOI：
10.3390/ijms241310561
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发表时间：
2023-06-23
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
目前还没有基因表达检测可以评估癌前病变是否会发展为浸润性乳腺癌。本研究旨在确定生物标志物，用于选择具有正常组织学、良性病变或癌前病变的乳腺浸润性癌高潜力患者。一组26个基因的mRNA表达谱被用来识别浸润性导管癌组织学正常组织和良性病变，并选择那些与非典型导管增生（ADH）相关的乳腺未来癌症发展（ADHC）的可能性更高。表达定义的模型在将浸润性导管癌从组织学正常组织和良性病变（n = 185）分类中实现了94.05%（AUC = 0.96）的总体准确性。该基因标记以100%的总体准确度（n = 8）对ADH组织中的癌症发展进行分类。使用独立组织样品（n = 77）和血液样品（n = 48）的RT-PCR分析来验证这26个基因的mRNA表达模式。免疫组化检测PBX 2和RAD 52蛋白表达可预测乳腺癌患者的生存结局。该特征在癌症基因组图谱乳腺癌患者（n = 1100）以及基底样和管腔A亚型中提供了显著的预后分层，并且与不同的免疫浸润和活性相关。26个基因的mRNA和蛋白表达与18种NCCN推荐的治疗乳腺癌的药物的敏感性或耐药性相关。11个基因在CRISPR-Cas9/RNAi筛选中具有显著的增殖潜力。基于这种基因表达特征，VEGFR抑制剂ZM-306416被发现作为治疗乳腺癌的新药。
There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.
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影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
22.7
作者：
Corsello, Steven M.;Nagari, Rohith T.;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
DOI：
10.1038/modpathol.2016.134
发表时间：
2016-11
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
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影响因子：
64.8
作者：
Garnett, Mathew J.;Edelman, Elena J.;Heidorn, Sonja J.;Greenman, Chris D.;Dastur, Anahita;Lau, King Wai;Greninger, Patricia;Thompson, I. Richard;Luo, Xi;Soares, Jorge;Liu, Qingsong;Iorio, Francesco;Surdez, Didier;Chen, Li;Milano, Randy J.;Bignell, Graham R.;Tam, Ah T.;Davies, Helen;Stevenson, Jesse A.;Barthorpe, Syd;Lutz, Stephen R.;Kogera, Fiona;Lawrence, Karl;McLaren-Douglas, Anne;Mitropoulos, Xeni;Mironenko, Tatiana;Thi, Helen;Richardson, Laura;Zhou, Wenjun;Jewitt, Frances;Zhang, Tinghu;O'Brien, Patrick;Boisvert, Jessica L.;Price, Stacey;Hur, Wooyoung;Yang, Wanjuan;Deng, Xianming;Butler, Adam;Choi, Hwan Geun;Chang, JaeWon;Baselga, Jose;Stamenkovic, Ivan;Engelman, Jeffrey A.;Sharma, Sreenath V.;Delattre, Olivier;Saez-Rodriguez, Julio;Gray, Nathanael S.;Settleman, Jeffrey;Futreal, P. Andrew;Haber, Daniel A.;Stratton, Michael R.;Ramaswamy, Sridhar;McDermott, Ultan;Benes, Cyril H.
通讯作者：
Benes, Cyril H.