Bramwell Vivien H C, Tuck Alan B, Wilson Sylvia M, Stitt Larry W, Cherian Anil K, Rorke Stewart C, Al-Katib Waleed, Postenka Carl O, Chambers Ann F
London Regional Cancer Program and Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Cancer Biol Ther. 2005 Dec;4(12):1336-41. doi: 10.4161/cbt.4.12.2166. Epub 2005 Dec 9.
There is a need for molecular markers that predict biological behavior of adult soft tissue tumors. Elevated levels of osteopontin (OPN) a transformation-linked protein, have been associated with poor survival in many cancers. OPN induces cell migration in cancer cells, in part through activation of the hepatocyte growth factor (HGF) receptor (Met) and its signaling pathway. Met expression has been associated with a poor prognosis in some sarcomas. In a series of 15 patients with adult soft tissue tumors, we found that mRNA levels of OPN (p=0.015), Met (p=0.03) and HGF (p<0.001) were significantly higher in tumor tissues relative to paired normal tissues. By immunohistochemistry, in tumor tissue from 33 patients, we demonstrated that increased expression of OPN, but not Met protein, was associated with higher stage (p=0.025) and grade (p=0.005). We found that increased expression of OPN, but not Met protein, was associated with decreased overall survival (p=0.008) at five years. This study, which is the first to examine coexpression of these two markers, suggests that OPN may have potential as a prognostic marker in adult soft tissue sarcomas, and further that OPN+/-Met signaling pathways may contribute to their biological behavior.
需要能够预测成人软组织肿瘤生物学行为的分子标志物。骨桥蛋白（OPN）是一种与转化相关的蛋白，其水平升高与多种癌症的不良生存相关。OPN部分通过激活肝细胞生长因子（HGF）受体（Met）及其信号通路诱导癌细胞迁移。Met表达与某些肉瘤的不良预后相关。在一组15例成人软组织肿瘤患者中，我们发现相对于配对的正常组织，肿瘤组织中OPN（p = 0.015）、Met（p = 0.03）和HGF（p < 0.001）的mRNA水平显著更高。通过免疫组织化学，在33例患者的肿瘤组织中，我们证明OPN表达增加而非Met蛋白表达增加与更高的分期（p = 0.025）和分级（p = 0.005）相关。我们发现OPN表达增加而非Met蛋白表达增加与五年总生存率降低（p = 0.008）相关。这项首次检测这两种标志物共表达的研究表明，OPN可能有潜力作为成人软组织肉瘤的预后标志物，进一步表明OPN + / - Met信号通路可能影响其生物学行为。
