Race-associated biological differences among Luminal A breast tumors.
Race-associated biological differences among Luminal A breast tumors.
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DOI：
10.1007/s10549-015-3474-4
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发表时间：
2015-07
影响因子：
3.8
通讯作者：
Troester MA
中科院分区：
文献类型：
--
作者：
D'Arcy M;Fleming J;Robinson WR;Kirk EL;Perou CM;Troester MA
非裔美国人（AA）女性的乳腺癌特异性死亡率较高。结果更差的基底细胞样乳腺癌亚型的患病率更高，但AA女性即使在更有利的结果中也有更高的死亡率。这些差异可能反映了治疗或卫生保健获取问题，固有的生物学差异，或两者兼而有之。为了确定Luminal A型乳腺癌中种族的潜在生物学差异，分析了来自108个CAU和57个AA乳腺肿瘤的基因表达数据。接下来评估种族相关基因与生存的关联。最后，在AA和CAU妇女的正常组织中评估种族和生存相关基因的表达。6个基因（ACOX 2、MUC 1、PSPH、SQLE、TYMS）在Luminal A型乳腺癌中按种族差异表达，并且与生存相关（HR < 0.8，HR > 1.25）。对于所有6个基因，AA中的肿瘤具有高表达的不良预后基因（PSABB 2，PSPH，SQLE，TYMS）和低表达的良好预后基因（ACOX 2，MUC 1）。基于所有六个基因的评分在大型独立数据集中预测存活率（HR = 1.9上四分位数与下四分位数，95%CI：1.4 - 2.5）。对于四个基因，AA和CAU妇女的正常组织显示出相似的表达（ACOX 2，MUC 1，SQLE，TYMS），然而，与AA相比，CAU妇女的正常组织中的不良结果相关基因PSPH和PSPBB 2的表达更高。该分析确定了可能导致死亡率差异的基因表达差异，并表明在管腔A型乳腺肿瘤中，AA和CAU患者之间存在生物学差异。这些差异中的一些（PSPBB 2和PSPH）可能存在于肿瘤发展的最早阶段，甚至在恶性肿瘤之前。
African American (AA) women have higher breast-cancer specific mortality rates. A higher prevalence of the worse outcome Basal-like breast cancer subtype contributes to this, but AA women also have higher mortality even within the more favorable outcomes Luminal A breast cancers. These differences may reflect treatment or health care access issues, inherent biological differences, or both. To identify potential biological differences by race among Luminal A breast cancers, gene expression data from 108 CAU and 57 AA breast tumors were analyzed. Race-associated genes were next evaluated for associations with survival. Finally, expression of race- and survival-associated genes was evaluated in normal tissue of AA and CAU women. Six genes (ACOX2, MUC1, CRYBB2, PSPH, SQLE, TYMS) were differentially expressed by race among Luminal A breast cancers and were associated with survival (HR < 0.8, HR > 1.25). For all six genes, tumors in AA had higher expression of poor prognosis genes (CRYBB2, PSPH, SQLE, TYMS) and lower expression of good prognosis genes (ACOX2, MUC1). A score based on all six genes predicted survival in a large independent dataset (HR = 1.9 top vs. bottom quartile, 95% CI: 1.4 – 2.5). For four genes, normal tissue of AA and CAU women showed similar expression (ACOX2, MUC1, SQLE, TYMS), however, the poor outcome associated genes CRYBB2 and PSPH were more highly expressed in AA vs. CAU women’s normal tissue. This analysis identified gene expression differences that may contribute to mortality disparities and suggests that among Luminal A breast tumors there are biological differences between AA and CAU patients. Some of these differences (CRYBB2 and PSPH) may exist from the earliest stages of tumor development, or even precede malignancy.