Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients.
Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients.
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DOI：
10.18632/oncotarget.2385
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发表时间：
2014-09-30
期刊：
影响因子：
--
通讯作者：
Trumpp A
中科院分区：
文献类型：
--
作者：
Baccelli I;Stenzinger A;Vogel V;Pfitzner BM;Klein C;Wallwiener M;Scharpff M;Saini M;Holland-Letz T;Sinn HP;Schneeweiss A;Denkert C;Weichert W;Trumpp A
虽然管腔型乳腺癌可以得到有效的治疗，但转移性疾病的发展仍然是一个重要的临床问题。我们之前已经证明，共表达酪氨酸激酶MET和CD47的管腔型循环肿瘤细胞(CTCs)能够启动异种移植瘤的转移。CD47是一种参与癌细胞逃避巨噬细胞清除的配体。在这里，我们通过免疫组织化学方法研究了255例激素受体阳性的乳腺肿瘤中MET-CD47共表达的临床相关性，发现MET-CD47双阳性和双阴性患者的平均总生存期有10.3年的差异(p<；0.001)。经多因素分析(COX比例风险模型：HR：4.1p<；0.002)，MET-CD47共同表达是一个新的独立预后因素，CD47单独表达或与MET联合表达与淋巴结转移密切相关。此外，对转移性患者血液的流式细胞术分析显示，MET+CD47+CTCs的存在始终如一(占CTCs的0.8-33.3%)，其频率与转移扩散的增加有关。最后，MET+CD47+含量高的原代未培养CTCs在小鼠体内启动转移的能力增强。因此，MET和CD47的检测和靶向可能为管腔型乳腺癌患者的风险分层和治疗提供合理的依据。
Although luminal-type primary breast cancer can be efficiently treated, development of metastatic disease remains a significant clinical problem. We have previously shown that luminal-type circulating tumor cells (CTCs) co-expressing the tyrosine-kinase MET and CD47, a ligand involved in cancer cell evasion from macrophage scavenging, are able to initiate metastasis in xenografts. Here, we investigated the clinical relevance of MET-CD47 co-expression in 255 hormone receptor positive breast tumors by immunohistochemistry and found a 10.3-year mean overall-survival difference between MET-CD47 double-positive and double-negative patients (p<0.001). MET-CD47 co-expression defined a novel independent prognosticator for overall-survival by multivariate analysis (Cox proportional hazards model: HR: 4.1, p<0.002) and CD47 expression alone or in combination with MET was strongly associated with lymph node metastasis. Furthermore, flow cytometric analysis of metastatic patient blood revealed consistent presence of MET+CD47+ CTCs (range 0.8 – 33.3% of CTCs) and their frequency was associated with increased metastatic spread. Finally, primary uncultured CTCs with high MET+CD47+ content showed an enhanced capacity to initiate metastasis in mice. Detection and targeting of MET and CD47 may thus provide a rational basis for risk stratification and treatment of patients with luminal-type breast cancer.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
11.2
作者：
Chao MP;Alizadeh AA;Tang C;Jan M;Weissman-Tsukamoto R;Zhao F;Park CY;Weissman IL;Majeti R
通讯作者：
Majeti R
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
64.5
作者：
Chao MP;Alizadeh AA;Tang C;Myklebust JH;Varghese B;Gill S;Jan M;Cha AC;Chan CK;Tan BT;Park CY;Zhao F;Kohrt HE;Malumbres R;Briones J;Gascoyne RD;Lossos IS;Levy R;Weissman IL;Majeti R
通讯作者：
Majeti R