Boonstra Martin C, Verbeek Floris P R, Mazar Andrew P, Prevoo Hendrica A J M, Kuppen Peter J K, van de Velde Cornelis J H, Vahrmeijer Alexander L, Sier Cornelis F M
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
BMC Cancer. 2014 Apr 17;14:269. doi: 10.1186/1471-2407-14-269.
The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. Within the tumor microenvironment uPAR is expressed by malignant cells as well as tumor-associated stromal cells. However, the contribution of uPAR expression in these stromal cells to malignancy and patient survival in colorectal cancer is still unclear. This study compares the association of uPAR expression in both colorectal tumor-associated stromal cells and neoplastic cells with clinico-pathological characteristics and patient survival using tissue micro arrays (TMA).
Immunohistochemical staining of uPAR expression was performed on tumor tissue from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and multivariate Cox's regression analyses were used to calculate associations between uPAR expression and patient survival.
In the colorectal tumor-associated stromal microenvironment, uPAR is expressed in macrophages, (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor-associated stromal cells and neoplastic cells (and both combined) were negatively associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and multivariate Cox's regression analysis for combined uPAR expression in tumor-associated stromal and neoplastic cells showed significant and independent negative associations with OS and DFS. Only uPAR expression in tumor-associated stromal cells showed independent significance in the uni- and multivariate analysis for DFS.
This study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells.
尿激酶型纤溶酶原激活物受体（uPAR）与癌症的发生和发展相关。在肿瘤微环境中，uPAR由恶性细胞以及肿瘤相关基质细胞表达。然而，这些基质细胞中uPAR表达对结直肠癌恶性程度和患者生存的影响仍不清楚。本研究使用组织微阵列（TMA）比较结直肠癌肿瘤相关基质细胞和肿瘤细胞中uPAR表达与临床病理特征及患者生存的相关性。
对262例结直肠癌患者的肿瘤组织进行uPAR表达的免疫组化染色。采用Kaplan-Meier法、对数秩检验以及单因素和多因素Cox回归分析来计算uPAR表达与患者生存之间的相关性。
在结直肠癌肿瘤相关基质微环境中，uPAR在巨噬细胞、（新生血管）内皮细胞和成肌纤维细胞中表达。肿瘤相关基质细胞和肿瘤细胞中uPAR的表达（以及两者的联合表达）与总生存期（OS）和无病生存期（DFS）呈负相关。对肿瘤相关基质细胞和肿瘤细胞中uPAR联合表达进行单因素和多因素Cox回归分析显示，其与OS和DFS存在显著且独立的负相关。仅肿瘤相关基质细胞中uPAR的表达在DFS的单因素和多因素分析中显示出独立的显著性。
本研究表明，结直肠癌患者生存与uPAR表达之间存在显著的独立负相关，尤其是在肿瘤相关基质细胞中。
