Differences in Gene and Protein Expression and the Effects of Race/Ethnicity on Breast Cancer Subtypes
Differences in Gene and Protein Expression and the Effects of Race/Ethnicity on Breast Cancer Subtypes
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DOI：
10.1158/1055-9965.epi-13-0929
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Gonzalez-Angulo, Ana M.
中科院分区：
文献类型：
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作者：
Chavez-MacGregor, Mariana;Liu, Shuying;Gonzalez-Angulo, Ana M.
背景资料：根据人种/种族和癌症亚型，乳腺癌之间基因或蛋白质表达模式的差异方法：使用Affytek HG-U133A平台在376例患者中进行转录谱分析，并对来自单独队列的255例患者中的177种蛋白质进行反相蛋白质阵列分析（RPPA）。进行无监督聚类，以及按种族和肿瘤亚型进行监督比较。标准的统计方法，BRB阵列工具，和Incidity Pathways软件包被用来分析data.Results：中位年龄为50岁，在两个队列。在RPPA队列中，54.5%的肿瘤为激素受体阳性（HR阳性），20.7%为HER2阳性，24.71%为三阴性（TNBC）。分别有147例（57.6%）、47例（18.43%）和46例（18.1%）患者为白色、西班牙裔和黑人。蛋白质表达数据的无监督分层聚类显示，按种族没有明显的聚类（HR阳性、HER2阳性和TNBC肿瘤的P值分别为0.492、0.489和0.494）。在基因表达队列中，54.2%的肿瘤为HR阳性，16.5%为HER2阳性，29.3%为TNBC。分别有216例（57.5%）、111例（29.52%）和32例（8.52%）患者为白色、西班牙裔和黑人。假发现率（FDR）<0.05的探针组均未显示乳腺癌亚型与种族的相关性;使用途径和基因组富集分析方法获得了类似的结果。结论：我们没有检测到不同种族/民族乳腺癌女性患者的RNA或蛋白质表达存在显著差异。影响：需要对导致种族/族裔之间结果差异的复杂因素网络进行更多研究。
Background: Differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype.Methods: Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. Standard statistical methods, BRB-Array tools, and Ingenuity Pathways software packages were used to analyze the data.Results: Median age was 50 years in both the cohorts. In the RPPA cohort, 54.5% of the tumors were hormone receptor-positive (HR-positive), 20.7% HER2-positive, and 24.71% triple-negative (TNBC). One hundred and forty-seven (57.6%), 47 (18.43%), and 46 (18.1%) of the patients were White, Hispanic, and Black, respectively. Unsupervised hierarchical clustering of the protein expression data showed no distinct clusters by race (P values were 0.492, 0.489, and 0.494 for the HR-positive, HER2-positive, and TNBC tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR-positive, 16.5% HER2-positive, and 29.3% TNBC. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were White, Hispanic, and Black, respectively. No probe set with a false discovery rate (FDR) of < 0.05 showed an association with race by breast cancer subtype; similar results were obtained using pathway and gene set enrichment analysis methods.Conclusions: We did not detect a significant variation in RNA or protein expression comparing different race/ethnicity groups of women with breast cancer.Impact: More research on the complex network of factors that result in outcomes differences among race/ethnicities is needed.