AR negative triple negative or "quadruple negative" breast cancers in African American women have an enriched basal and immune signature.
AR negative triple negative or "quadruple negative" breast cancers in African American women have an enriched basal and immune signature.
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DOI：
10.1371/journal.pone.0196909
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Yates C
中科院分区：
文献类型：
--
作者：
Davis M;Tripathi S;Hughley R;He Q;Bae S;Karanam B;Martini R;Newman L;Colomb W;Grizzle W;Yates C
越来越多的证据表明，雄激素受体（AR）的表达在三阴性乳腺癌（TNBC）中具有预后价值，其中缺乏AR表达的肿瘤被视为“四阴性”乳腺癌（“QNBC”）。然而，尚未有对所有乳腺癌亚型中或按种族分层的AR表达进行综合分析的报道。我们评估了癌症基因组图谱（TCGA）中925个肿瘤以及2个验证组中136个肿瘤的AR mRNA表达。通过免疫组织化学方法测定了来自一个多机构队列的197个肿瘤的AR蛋白表达，总共分析了1258名患者。考克斯风险比用于确定与PAM50乳腺癌亚型以及TNBC亚型的相关性。总体而言，与AR阳性患者相比，AR阴性患者确诊时年龄更小，非裔美国人（AA）AR阴性患者的平均年龄为49岁。与白人相比，非裔美国人的乳腺肿瘤AR表达率较低，且与雌激素受体（ER）和孕激素受体（PR）的表达无关（p<0.0001）。与其他PAM50亚型相比，AR阴性患者为基底样亚型的比值比为（66.60；95%置信区间，32 - 146），这与疾病进展时间延长和总生存期缩短有关。非裔美国人“四阴性”乳腺癌患者主要表现为BL1、BL2和IM亚型，与白人患者相比，E2F1、NFKBIL2、CCL2、TGFB3、CEBPB、PDK1、IL12RB2、IL2RA和SOS1基因表达存在差异。免疫检查点抑制剂PD - 1、PD - L1和CTLA - 4在总体“四阴性”乳腺癌患者以及非裔美国人“四阴性”乳腺癌患者中均显著上调。因此，AR可作为乳腺癌的一个预后标志物，特别是在非裔美国人“四阴性”乳腺癌患者中。
There is increasing evidence that Androgen Receptor (AR) expression has prognostic usefulness in Triple negative breast cancer (TNBC), where tumors that lack AR expression are considered “Quadruple negative” Breast Cancers (“QNBC”). However, a comprehensive analysis of AR expression within all breast cancer subtypes or stratified by race has not been reported. We assessed AR mRNA expression in 925 tumors from The Cancer Genome Atlas (TCGA), and 136 tumors in 2 confirmation sets. AR protein expression was determined by immunohistochemistry in 197 tumors from a multi-institutional cohort, for a total of 1258 patients analyzed. Cox hazard ratios were used to determine correlations to PAM50 breast cancer subtypes, and TNBC subtypes. Overall, AR-negative patients are diagnosed at a younger age compared to AR-positive patients, with the average age of AA AR-negative patients being, 49. AA breast tumors express AR at lower rates compared to Whites, independent of ER and PR expression (p<0.0001). AR-negative patients have a (66.60; 95% CI, 32–146) odds ratio of being basal-like compared to other PAM50 subtypes, and this is associated with an increased time to progression and decreased overall survival. AA “QNBC” patients predominately demonstrated BL1, BL2 and IM subtypes, with differential expression of E2F1, NFKBIL2, CCL2, TGFB3, CEBPB, PDK1, IL12RB2, IL2RA, and SOS1 genes compared to white patients. Immune checkpoint inhibitors PD-1, PD-L1, and CTLA-4 were significantly upregulated in both overall “QNBC” and AA “QNBC” patients as well. Thus, AR could be used as a prognostic marker for breast cancer, particularly in AA “QNBC” patients.
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影响因子：
4.4
作者：
Sørlie T;Wang Y;Xiao C;Johnsen H;Naume B;Samaha RR;Børresen-Dale AL
通讯作者：
Børresen-Dale AL
影响因子：
3.7
作者：
Martin, Damali N.;Boersma, Brenda J.;Yi, Ming;Reimers, Mark;Howe, Tiffany M.;Yfantis, Harry G.;Tsai, Yien Che;Williams, Erica H.;Lee, Dong H.;Stephens, Robert M.;Weissman, Allan M.;Ambs, Stefan
通讯作者：
Ambs, Stefan
影响因子：
--
作者：
Jiang HS;Kuang XY;Sun WL;Xu Y;Zheng YZ;Liu YR;Lang GT;Qiao F;Hu X;Shao ZM
通讯作者：
Shao ZM
影响因子：
2.1
作者：
Hardiman, Gary;Savage, Stephen J.;Gattoni-Celli, Sebastiano
通讯作者：
Gattoni-Celli, Sebastiano
影响因子：
5.8
作者：
Polpitiya, Ashoka D.;Qian, Wei-Jun;Smith, Richard D.
通讯作者：
Smith, Richard D.