Märkl Bruno, Hardt Jochen, Franz Simon, Schaller Tina, Schenkirsch Gerhard, Kriening Bernadette, Hoffmann Reinhard, Rüth Stefan
Institute of Pathology, Klinikum Augsburg, Augsburg, Germany.
Institute of Laboratory Medicine and Microbiology, Klinikum Augsburg, Augsburg, Germany.
Gastroenterol Res Pract. 2017;2017:6504960. doi: 10.1155/2017/6504960. Epub 2017 Feb 12.
. The prognostic role of the proteases uPA and PAI-1, as well as tumor budding, in colon cancer, has been investigated previously. . We provide 6-year follow-up data and results of the validation set. The initial test set and validation set consisted of 55 colon cancers and 68 colorectal cancers, respectively. Tissue samples were analyzed for uPA and PAI-1 using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Tumor budding was analyzed on cytokeratin-stained slides. Survival analyses were performed using cut-offs that were determined previously. . uPA was not prognostic for outcome. PAI-1 showed a trend towards reduced cancer specific survival in PAI-1 high-grade cases (68 versus 83 months; = 0.091). The combination of high-grade PAI-1 and tumor budding was associated with significantly reduced cancer specific survival (60 versus 83 months; = 0.021). After pooling the data from both sets, multivariate analyses revealed that the factors pN-stage, V-stage, and a combination of tumor budding and PAI-1 were independently prognostic for the association with distant metastases. . A synergistic adverse effect of PAI-1 and tumor budding in uni- and multivariable analyses was found. PAI-1 could serve as a target for anticancer therapy.
蛋白酶尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂-1（PAI-1）以及肿瘤芽生在结肠癌中的预后作用此前已被研究。我们提供了6年的随访数据和验证集的结果。初始测试集和验证集分别由55例结肠癌和68例结直肠癌组成。使用市售的酶联免疫吸附测定（ELISA）分析组织样本中的uPA和PAI-1。在细胞角蛋白染色的玻片上分析肿瘤芽生。使用先前确定的临界值进行生存分析。uPA对预后无预测价值。PAI-1在PAI-1高分级病例中显示出癌症特异性生存率降低的趋势（68个月对83个月；P = 0.091）。高分级PAI-1与肿瘤芽生的联合与癌症特异性生存率显著降低相关（60个月对83个月；P = 0.021）。合并两组数据后，多变量分析显示pN分期、V分期以及肿瘤芽生和PAI-1的联合是远处转移相关性的独立预后因素。在单变量和多变量分析中发现PAI-1和肿瘤芽生具有协同不良影响。PAI-1可作为抗癌治疗的靶点。
