Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts
Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts
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DOI：
10.1002/path.2071
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发表时间：
2006-12-01
影响因子：
7.3
通讯作者：
Isacke, C. M.
中科院分区：
文献类型：
--
作者：
Esseghir, S.;Reis, J. S.;Isacke, C. M.
这项研究表明，通过严格的筛选方法和彻底的验证相结合，有可能确定跨膜蛋白优先表达在原发性乳腺肿瘤细胞。从分离自浸润性乳腺癌的肿瘤细胞中提取mRNA，然后将其与正常乳腺组织mRNA相减，然后生成信号序列捕获文库。筛选文库，鉴定出31个阳性克隆，编码12种细胞表面蛋白和12种分泌蛋白。跨膜基因的表达的一个子集，然后询问使用高通量的方法（组织微阵列）加上尖端原位技术在一个大的队列的患者谁经历了统一的辅助化疗。在整个队列中，CD 98重链（CD 98 HC）表达和胰岛素样生长因子2受体/甘露糖-6-磷酸受体（IGF 2 R1 M6 PR）低水平表达与患者预后不良相关。缓激肽受体B1（BDKRB 1）和睾丸增强基因转录本（TEGT）的表达与雌激素受体（ER）阴性乳腺肿瘤患者的良好预后相关。这些结果表明，这种分离原发性肿瘤细胞，产生一个专门分离信号序列的转录本，并在组织微阵列原位杂交的组合方法成功地确定了新的预后标志物（BDKRB 1，CD 98 hc，和TEGT）和潜在的跨膜治疗靶点（CD 98 hc）在乳腺癌。版权所有（c）2006大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
This study demonstrates, through a combination of stringent screening methods and thorough validation, that it is possible to identify transmembrane proteins preferentially expressed in primary breast tumour cells. mRNA was extracted from tumour cells isolated from invasive breast cancers and it was then subtracted against normal breast tissue mRNA prior to the generation of a signal sequence-trap library. Screening of the library identified 31 positive clones encoding 12 cell-surface and 12 secreted proteins. The expression of a subset of transmembrane genes was then interrogated using a high-throughput method (tissue microarray) coupled with cutting-edge in situ techniques in a large cohort of patients who had undergone uniform adjuvant chemotherapy. Expression of CD98 heavy chain (CD98HC) and low-level expression of the insulin-like growth factor 2 receptor/mannose-6-phosphate receptor (IGF2R1M6PR) correlated with poor patient prognosis in the whole cohort. Expression of bradykinin receptor B1 (BDKRB1) and testis enhanced gene transcript (TEGT) correlated with good prognosis in woman with oestrogen receptor (ER)-negative breast tumours. These results indicate that this combined approach of isolating primary tumour cells, generating a library to specifically isolate signal-sequence-containing transcripts, and in situ hybridization on tissue microarrays successfully identified novel prognostic markers (BDKRB1, CD98hc, and TEGT) and potential transmembrane therapeutic targets (CD98hc) in breast cancer. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.