Zhang Lijian, Chen Jinfeng, Ke Yang, Mansel Robert E, Jiang Wen G
Department of Surgery, Peking University School of Oncology, Haidian District, Beijing, PR China.
Int J Mol Med. 2006 May;17(5):937-44.
Angiogenesis is under the exquisite control of a network of angiogenic factors and anti-angiogenic factors. PEDF (pigment epithelial derived factor) is one of the known anti-angiogenesis factors and is naturally occurring in the body. There has been studies to show that the factor plays an important role in negating the angiogenic process in pathological conditions in the eye. However, little is known about its expression in solid tumors. The current study examined PEDF expression at protein and message levels and investigated its critical link with cancer progression and prognosis in patients with non-small cell lung cancer (NSCLC). We used immunohistochemistry to examine the protein expression of PEDF and to evaluate the microvessel density (MVD) in a cohort of 91 NSCLC patients. In addition, real-time quantitative PCR was used to measure levels of the PEDF transcript. PEDF was positively stained in cytoplasm of cancer cells, but at a lower level, compared with normal cells in the lung tissues. Low levels of PEDF were seen in 57.1% patients. The levels of PEDF appeared to be associated with MVD, in that patients with reduced PEDF had a significantly high MVD count (28.50), compared with patients with high levels of PEDF who had a 16.98 MVD count (p<0.0005). In univariate but not multivariate analysis PEDF was an independent prognostic factor. In real-time PCR analysis, PEDF mRNA level of cancer tissue was significantly lower than normal tissue (0.55+/-0.36 vs 0.72+/-0.26, p=0.024, paired t-test). PEDF mRNA level in cancer tissue was negatively associated with TNM stage and the tumor size (p<0.05, independent t-test). Finally, low levels of PEDF in lung tumor tissues was associated with a significantly shorter survival (p=0.038) using Kaplan-Meier and Cox analyses. In this first study, PEDF was reduced at both protein and mRNA level in NSCLC tumors compared with normal lung tissues. This reduction is associated with an increase in microvessel density in tumors and significantly associated with TNM stage, tumor size and the overall survival. PEDF is an important factor in NSCLC development and may be a of prognostic value for NSCLC patients.
血管生成受血管生成因子和抗血管生成因子网络的精确调控。色素上皮衍生因子（PEDF）是已知的抗血管生成因子之一，在体内天然存在。已有研究表明，该因子在抑制眼部病理状态下的血管生成过程中发挥重要作用。然而，关于其在实体瘤中的表达情况却知之甚少。本研究检测了非小细胞肺癌（NSCLC）患者中PEDF在蛋白和信使水平的表达，并探讨了其与癌症进展及预后的关键联系。我们采用免疫组化方法检测了91例NSCLC患者队列中PEDF的蛋白表达，并评估了微血管密度（MVD）。此外，运用实时定量PCR检测PEDF转录本水平。与肺组织中的正常细胞相比，癌细胞胞质中PEDF呈阳性染色，但水平较低。57.1%的患者PEDF水平较低。PEDF水平似乎与MVD相关，PEDF水平降低的患者微血管密度计数显著较高（28.50），而PEDF水平较高的患者微血管密度计数为16.98（p<0.0005）。在单因素分析而非多因素分析中，PEDF是一个独立的预后因素。在实时PCR分析中，癌组织的PEDF mRNA水平显著低于正常组织（0.55±0.36对0.72±0.26，p=0.024，配对t检验）。癌组织中的PEDF mRNA水平与TNM分期及肿瘤大小呈负相关（p<0.05，独立t检验）。最后，运用Kaplan-Meier和Cox分析发现，肺肿瘤组织中PEDF水平较低与生存期显著缩短相关（p=0.038）。在这项首次研究中，与正常肺组织相比，NSCLC肿瘤中PEDF在蛋白和mRNA水平均降低。这种降低与肿瘤微血管密度增加相关，并与TNM分期、肿瘤大小及总生存期显著相关。PEDF是NSCLC发展中的一个重要因素，可能对NSCLC患者具有预后价值。
