EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer.
EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer.
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DOI：
10.1038/bjc.2012.293
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发表时间：
2012-08-07
影响因子：
8.8
通讯作者：
Flatmark, K.
中科院分区：
文献类型：
--
作者：
Boye, K.;Nesland, J. M.;Sandstad, B.;Haugen, M. Haugland;Mlandsmo, G. M.;Flatmark, K.
蛋白水解酶及其调节因子通过刺激大肠癌的侵袭和转移在大肠癌中具有重要的生物学作用，这使得这些因子作为潜在的预后生物标志物具有吸引力。采用免疫组织化学方法对277例前瞻性招募的结直肠癌患者的原发性肿瘤中细胞外基质金属蛋白酶诱导物（EMMPRIN）的表达进行了表征，并研究了其与S100A4表达、临床病理参数和患者结局的相关性。198例（72%）显示肿瘤细胞膜染色阳性，而10例（4%）为临界阳性。在单变量和多变量分析中，EMMPRIN表达与较短的无转移、疾病特异性和总生存期相关。预后影响主要局限于TNM III期，EMMPRIN阴性的III期患者预后良好。此外，EMMPRIN与S100A4的表达显著相关，并且这些生物标志物的联合表达赋予甚至更差的预后。然而，在SiRNA敲除实验中，没有证据表明结直肠癌细胞系HCT 116和SW 620中这两种蛋白质之间存在直接调节。EMMPRIN是结直肠癌的一个有前途的预后生物标志物，我们的研究结果表明，它可以用于选择III期患者进行辅助治疗。
Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy.
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影响因子：
6.4
作者：
Hilska, Marja;Roberts, Peter J.;Laato, Matti
通讯作者：
Laato, Matti
影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
11.5
作者：
Reimers, N;Zafrakas, K;Pantel, K
通讯作者：
Pantel, K
影响因子：
6.4
作者：
Li, Yu;Xu, Jing;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan
影响因子：
--
作者：
Boe, S.;Longva, A. S.;Hovig, E.
通讯作者：
Hovig, E.