Akın Kabalak Pınar, Çiledağ Aydın, Demir Nalan, Çelik Gökhan, Yüksel Cabir, Köycü Gözde, Gökmen Öztuna Derya, Taner Abbas, Kaya Akın, Kutlay Hakan, Numanoğlu Numan, Savaş İsmail
Department of Chest Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey.
Tuberk Toraks. 2015 Jun;63(2):71-7. doi: 10.5578/tt.9015.
Vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) are major angiogenic mediators in neovascularization process. In current literature both biomarkers are discussed separately and only for non-small cell lung cancer (NSCLC). So in this study we aimed to examine them together for both cell types NSCLC and small cell lung cancer (SCLC).
100 patients with lung cancer were enrolled to this single center study. 87 of patients were diagnosed with NSCLC including 28 adenocarcinomas and 59 squamous cell cancers and 13 were SCLC. Results were compared with 30 healthy volunteers. Pre-treatment serum VEGF and Ang-2 levels were measured by using ELISA method.
While serum Ang-2 levels were higher in patients than healthy controls (23395 pg/mL vs. 4025 pg/mL, p< 0.001), VEGF levels didn't differ (2308 pg/mL vs. 2433 pg/mL, p> 0.05). There was no difference between cases with SCLC and NSCLC in terms of Ang-2. But serum VEGF values were significantly lower in SCLC than NSCLC and control groups. None of these mediators were correlated with cell type, tumor size, TNM staging, performance status and operability. VEGF levels were higher in patients with chronic obstructive pulmonary disease (COPD), but it was not significant. Three cut of values were determined according to sensitivity and specificity by using youden index. They were 8515.73 pg/mL (sensitivity 78%, specificity 76%), 7097 pg/mL (sensitivity 80%, specificity 70%) and 11063.48 pg/mL (sensitivity 76%, specificity 70%). Patients with SCLC had shorter survival time above cut-off values (p> 0.05). VEGF and Ang-2 showed a weak positive correlation (p= 0.1 and r= 0.638).
In conclusion, serum VEGF wasn't useful to predict lung cancer, prognosis or cell type. Albeit Ang-2 was higher in patients with lung cancer without any effect on survival. Due to the heterogeneity of the studies done with serum measurement Ang-2 on tumor tissue should be more meaningful.
血管内皮生长因子(VEGF)和血管生成素-2(Ang-2)是新生血管形成过程中的主要血管生成介质。在当前文献中,这两种生物标志物是分别讨论的,且仅针对非小细胞肺癌(NSCLC)。因此,在本研究中,我们旨在对NSCLC和小细胞肺癌(SCLC)这两种细胞类型同时进行检测。
100例肺癌患者纳入本单中心研究。其中87例患者被诊断为NSCLC,包括28例腺癌和59例鳞状细胞癌,13例为SCLC。将结果与30名健康志愿者进行比较。采用酶联免疫吸附测定(ELISA)法检测治疗前血清VEGF和Ang-2水平。
患者血清Ang-2水平高于健康对照组(23395 pg/mL对4025 pg/mL,p<0.001),而VEGF水平无差异(2308 pg/mL对2433 pg/mL,p>0.05)。SCLC和NSCLC患者的Ang-2水平无差异。但SCLC患者的血清VEGF值显著低于NSCLC患者和对照组。这些介质均与细胞类型、肿瘤大小、TNM分期、体能状态和可手术性无关。慢性阻塞性肺疾病(COPD)患者的VEGF水平较高,但差异不显著。利用约登指数根据敏感性和特异性确定了三个临界值。分别为8515.73 pg/mL(敏感性78%,特异性76%)、7097 pg/mL(敏感性80%,特异性70%)和11063.48 pg/mL(敏感性76%,特异性70%)。SCLC患者在临界值以上的生存时间较短(p>0.05)。VEGF和Ang-2呈弱正相关(p=0.1,r=0.638)。
总之,血清VEGF对预测肺癌、预后或细胞类型并无帮助。尽管肺癌患者的Ang-2水平较高,但对生存无任何影响。由于血清测量研究的异质性,对肿瘤组织进行Ang-2检测可能更有意义。