A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma.
A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma.
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DOI：
10.1186/s12885-016-3030-6
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发表时间：
2017-01-04
期刊：
影响因子：
3.8
通讯作者：
Pontén F
中科院分区：
文献类型：
--
作者：
Gremel G;Djureinovic D;Niinivirta M;Laird A;Ljungqvist O;Johannesson H;Bergman J;Edqvist PH;Navani S;Khan N;Patil T;Sivertsson Å;Uhlén M;Harrison DJ;Ullenhag GJ;Stewart GD;Pontén F
对于肾细胞癌（RCC）的更好的预后和诊断工具存在未满足的临床需求。人类蛋白质图谱数据资源，包括正常和恶性人体组织的转录组和蛋白质组，搜索RCC特异性蛋白质和cubilin（CUBN）确定为候选者。将代表各种癌症类型的患者组织构建成组织微阵列（n = 940），并使用免疫组织化学研究RCC中CUBN表达与其他癌症相比的特异性。分析了两个独立的RCC队列（n = 181; n = 114），以进一步确定CUBN作为RCC特异性标志物的敏感性，并探索缺乏CUBN表达的RCC的分数是否可以预测患者生存率的差异。CUBN被鉴定为高度RCC特异性蛋白，使用免疫组织化学法，所有原发性RCC中有58%的CUBN染色阳性。在静脉肿瘤血栓和转移灶中，CUBN表达的频率逐渐丧失。与CUBN阴性肿瘤患者相比，CUBN阳性肿瘤的透明细胞RCC（ccRCC）患者的预后显著更好，与T分期、Fuhrman分级和淋巴结状态无关（HR 0.382，CI 0.203-0.719，P = 0.003）。CUBN表达对RCC具有高度特异性，并且蛋白质的丢失与不良预后显著且独立相关。ccRCC中CUBN的表达为ccRCC患者提供了一个有希望的积极预后指标。CUBN在RCC中表达的高特异性也表明其在临床癌症鉴别诊断中作为一种新的诊断标志物来确认或排除RCC。本文的在线版本（doi：10.1186/s12885-016-3030-6）包含补充材料，可供授权用户使用。
There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC). Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival. CUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203–0.719, P = 0.003). CUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC. The online version of this article (doi:10.1186/s12885-016-3030-6) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Laird A;O'Mahony FC;Nanda J;Riddick AC;O'Donnell M;Harrison DJ;Stewart GD
通讯作者：
Stewart GD
影响因子：
5.5
作者：
Gekle, M;Knaus, P;Christensen, EI
通讯作者：
Christensen, EI
影响因子：
5.6
作者：
Laury, Anna R.;Perets, Ruth;Hirsch, Michelle S.
通讯作者：
Hirsch, Michelle S.
影响因子：
6.4
作者：
Gremel, Gabriela;Bergman, Julia;Ponten, Fredrik
通讯作者：
Ponten, Fredrik
影响因子：
6.6
作者：
O'Hurley G;Sjöstedt E;Rahman A;Li B;Kampf C;Pontén F;Gallagher WM;Lindskog C
通讯作者：
Lindskog C