Colorectal Surgery Department, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
Int J Colorectal Dis. 2011 May;26(5):593-601. doi: 10.1007/s00384-011-1164-1. Epub 2011 Mar 15.
Tissue factor (TF) is emphasized as the promising target in the future targeted therapy strategy for colorectal cancer (CRC). Recent evidence showed that TF expression is under the control of K-ras and p53. However, a comprehensive evaluation of TF expression, K-ras status, and p53 mutation has not been systematically analyzed. The aims of this study were to identify the percentages of positive TF in CRC patients; analyze the associations of TF expression, K-ras status, and p53 mutation; and evaluate the prognostic value of TF in CRC patients.
Ninety-six CRC samples were tested for TF expression, p53 mutation, and K-ras status by semiquantitative immunohistochemistry, Western blotting analysis, direct sequencing, and real-time quantitative PCR. Associations were sought with TF expression and clinical outcomes.
TF expression was related to clinical stages, tumor differentiation, and tumor size. The positive proportions of TF expression on tumor cells and tumor vascular endothelial cells were 70% and 53% respectively in CRC patients. The positive proportion of TF co-expression on both cancer cells and tumor vascular endothelial cells was 40%, compared to an 83% total TF positive proportion in CRC patients. TF expression on CRC appeared to be increased with K-ras and/or p53 mutation(s). Disease-free survival and overall survival were significantly reduced in CRC patients with high TF expression.
TF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis and could be considered as a prognostic indicator for patients CRC.
组织因子（TF）被强调为结直肠癌（CRC）未来靶向治疗策略中有希望的靶点。最近的证据表明，TF 的表达受 K-ras 和 p53 的控制。然而，TF 表达、K-ras 状态和 p53 突变的综合评估尚未系统分析。本研究的目的是确定 CRC 患者 TF 阳性率；分析 TF 表达、K-ras 状态和 p53 突变之间的关联；并评估 TF 在 CRC 患者中的预后价值。
采用半定量免疫组织化学、Western blot 分析、直接测序和实时定量 PCR 检测 96 例 CRC 样本的 TF 表达、p53 突变和 K-ras 状态。寻找与 TF 表达和临床结果的关联。
TF 表达与临床分期、肿瘤分化和肿瘤大小有关。CRC 患者肿瘤细胞和肿瘤血管内皮细胞 TF 表达的阳性比例分别为 70%和 53%。CRC 患者中 TF 共表达在癌细胞和肿瘤血管内皮细胞上的阳性比例为 40%，而总 TF 阳性比例为 83%。TF 在 CRC 中的表达似乎随着 K-ras 和/或 p53 突变的增加而增加。高 TF 表达的 CRC 患者无病生存率和总生存率显著降低。
TF 可能参与了结直肠癌发生过程中的 K-ras 和 p53 突变，并可作为 CRC 患者的预后指标。
