Differences in the tumor microenvironment between African-American and European-American breast cancer patients.
Differences in the tumor microenvironment between African-American and European-American breast cancer patients.
复制标题
DOI：
10.1371/journal.pone.0004531
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Ambs, Stefan
中科院分区：
文献类型：
--
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
非洲裔美国乳腺癌患者的死亡率高于欧洲裔美国患者，尽管其发病率较低。我们测试了肿瘤生物学的内在差异可能导致这种癌症健康差异的假设。使用激光捕获显微切割技术，我们检测了18名非洲裔美国人和17名欧洲裔美国人患者肿瘤上皮和肿瘤间质特异性的全基因组mRNA表达。这两个患者组之间有许多基因的差异表达，并且在肿瘤上皮中有两个基因的签名将它们区分开来。为了鉴定肿瘤中因种族/民族而不同的生物学过程，进行了基因本体论和疾病关联分析。确定了几个生物过程，这可能有助于增强疾病的侵袭性，在非洲裔美国患者，包括血管生成和趋化性。非裔美国人的肿瘤也含有显著的干扰素特征。血管生成在非裔美国人肿瘤生物学中的作用通过检查248个乳腺肿瘤的血管化和巨噬细胞浸润的程度来进一步研究。免疫组化显示，微血管密度和巨噬细胞浸润是较高的肿瘤的非洲裔美国人比欧洲裔美国人。最后，使用计算机模拟方法，我们探索了基于基因表达谱为非洲裔美国患者量身定制治疗方案的潜力。这种探索性方法产生了可能对非洲裔美国人患者的肿瘤具有特异性拮抗活性的治疗剂列表，例如，西罗莫司、白藜芦醇和氯丙嗪治疗雌激素受体阴性肿瘤。乳腺肿瘤的基因表达谱表明，非洲裔美国人和欧洲裔美国人患者之间可能存在肿瘤生物学差异，超出了目前标记物的知识。值得注意的是，与肿瘤血管生成和趋化性相关的途径在这两个患者组中可能在功能上不同。
African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors. The gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers. Notably, pathways related to tumor angiogenesis and chemotaxis could be functionally different in these two patient groups.
登录
查看更多内容
影响因子：
3.7
作者：
Brodsky LI;Wahed AS;Li J;Tavis JE;Tsukahara T;Taylor MW
通讯作者：
Taylor MW
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1016/s0197-2456(98)00037-3
发表时间：
1998-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Dupont, WD;Plummer, WD
通讯作者：
Plummer, WD
影响因子：
11.5
作者：
Curran, Edward M.;Judy, Barbara M.;Estes, D. Mark
通讯作者：
Estes, D. Mark
影响因子：
3.1
作者：
Hayanga, Aworl J.;Newman, Lisa A.
通讯作者：
Newman, Lisa A.