血管内皮细胞生长因子在非小细胞肺癌中的表达

目的探讨血管内皮细胞生长因子(VEGF)、肿瘤微血管密度(MVD)2项指标与非小细胞肺癌各临床病理因素之间的关系以及两者之间的联系。方法采用免疫组织化学SABC法检测经病理检查确诊的68例非小细胞肺癌、13例癌旁和13例正常肺上皮组织VEGF、FVⅢ因子相关抗原的表达,对FVⅢ因子相关抗原标记的血管计数MVD。结果肺癌组织VEGF阳性表达率和MVD值明显高于正常肺上皮组织和癌旁组织;肿瘤直径≥5.0cm者MVD值明显高于直径<5.0cm者;腺癌MVD值明显高于鳞癌;有远处器官转移的肺癌MVD值明显高于无远处器官转移者;Ⅳ期肺癌MVD值明显高于Ⅰ期和Ⅱ期者,Ⅲ期MVD明显高于Ⅰ期,MVD值随TNM分期增加有逐渐增高的趋势;VEGF表达阳性的肺癌MVD值明显高于表达阴性者,并且随着VEGF表达程度的加强,MVD值增加。结论血管生成与肺癌的生长、浸润、转移及疾病进展密切相关;肺癌组织VEGF阳性表达率明显增加,是肺癌血管形成和维持的重要因子之一;MVD可作为判断非小细胞肺癌生物学行为,预测其发生发展的1项指标。     

Prognostic Impact of Elevation of Vascular Endothelial Growth Factor Family Expression in Patients with Non-small Cell lung Cancer: an Updated Meta-analysis

Background: The vascular endothelial growth factor family has been implicated in tumorigenesis andmetastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/VEGFR co-expression, in patients with non-small lung cancer remains controversial. Materials and Methods:Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluatingexpression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligiblefor inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled byusing a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. Results:74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, theexpression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) wasassociated separately with poor survival. Especially, VEGFA over-expression was an independent prognosticfactor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137).Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worsesurvival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicteda poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferableprognostic marker. Conclusions: The expression of VEGFA (particularly in SCC and early stage NSCLC),VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable asprognostic biologic markers.     

Disease Flare After EGFR Tyrosine Kinase Inhibitor Cessation Predicts Poor Survival in Patients with Non-small Cell Lung Cancer

Available study revealed non-small cell lung cancer (NSCLC) patients faced a risk of disease flare after cessation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There was no data concerning the prognostic value of disease flare. This study aimed to investigate the prevalence of disease flare in a Chinese cohort, and analyzed its prediction to survival. A cohort of 227 NSCLC patients with acquired resistance to EGFR TKI was retrospectively analyzed. Prevalence and clinical features of disease flare after TKI cessation were reviewed. Survival data were analyzed between patients with flare and those without flare. EGFR gene mutations in tumors were detected. Twenty of 227 (8.8 %) patients were determined with disease flare after TKI cessation. The median interval from TKI cessation to disease flare was 7 days (range 3–18). Forty percent of patients complained of deteriorated dyspnea attributable to malignant effusion. Thirty percent of patients had progressive lesions in the brain. After TKI cessation 35 % of flare patients died before challenge of subsequent treatment. No response was observed in 30 % of flare patients undergoing subsequent chemotherapy. When compared with the non-flare group, patients with disease flare demonstrated comparable progression-free survival (10.1 vs. 9.9 months; P?=?0.973), shorter post-TKI survival (4.1 vs. 6.1 months; P?<?0.001), and a significantly poor overall survival (16.6 vs. 21.6 months; P?=?0.002). Disease flare after cessation of EGFR TKI occurred in Chinese NSCLC population and predicted a poor survival.     

血管内皮生长因子、碱性成纤维细胞生长因子在非小细胞肺癌中的表达及临床意义

目的：探讨血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF)在非小细胞肺癌（Non-small cell lung cancer,NSCLC)中的表达及临床意义。方法：应用免疫组织化学方法检测96例NSCLC组织中VEGF、bFGF蛋白水平的表达，其中36例应用RT－PCR技术检测上述基因mRNA表达。结果：NSCLC中VEGF mRNA主要表达分泌性VEGF121和VEGF165，阳性率分别为69．5％（25／36）和41．7％（15／36），bFGF mRNA阳性率为52．8％（19／36）；免疫组化显示VEGF、bFGF阳性表达率分别为55．6％（20／36）和58．3％（21／36），二者之间呈正相关（P＝0．002）；VEGF、bFGF表达与患者年龄、性别、病理类型、分化程度、TNM分期、肿瘤转移、生存期等临床资料之间无统计学意义。结论：VEGF、bFGF在NSCLC血管形成中起重要作用，且二者具有协同作用。     

Serum BMP-2 Up-regulation as an Indicator of Poor Survival in Advanced Non-small Cell Lung Cancer Patients

Purpose: High levels of bone morphogenetic protein (BMPs) have been reported in patients with lung cancer.This study was conducted to assess correlations between serum BMP-2 levels and prognostic outcome in patientswith non-small-cell lung cancer (NSCLC). Methods: Blood samples from 84 patients with advanced NSCLCand 42 healthy controls were analyzed and quantitated for serum BMP-2 levels before and after two cycles ofchemotherapy using a commercially available ELISA kit. Results: The median level of BMP-2 was 146.9 pg/ml in patients with NSCLC vs. 87.7 pg/ml in healthy controls (P<0.01). A significant correlation was observedbetween pretreatment serum BMP-2 level and ECOG PS, disease stage and number of organs with metastases(P<0.05). Serum BMP-2 level decreased significantly in patients who achieved objective response after twocycles of chemotherapy. Multivariate analysis showed that increased BMP-2 level and advanced clinical stagewere significantly correlated with poor prognosis. Conclusion: Thes erum BMP-2 level is positively correlatedwith clinical stage, ECOG PS and metastatic burden and may serve as an independent negative predictor forprognosis. Decreased BMP-2 after chemotherapy could be a reliable marker for efficacy of treatment.     

AKT2在非小细胞肺癌中的表达及预后意义

背景与目的 AKT2是PI3K信号传导通路中重要因子,AKT2激活导致细胞生长和生存,近年来,许多研究表明AKT2在肿瘤形成、生长及转移中起着重要作用。本研究通过检测肿瘤组织中AKT2的表达水平,旨在研究AKT2在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其与临床预后的关系。方法通过免疫组化方法检测80例NSCLC及10例肺良性病变的组织标本中AKT2蛋白水平。结果 NSCLC中AKT2表达的阳性率为57.50%(46/80),明显高于肺良性病变组织(1/10,10.0%)中的表达,具有统计学差异(χ2=8.038,P=0.006)。AKT2表达与NSCLC患者临床病理特征无明显关系。AKT2表达与患者无进展生存期(χ2=12.671,P=0.005)及总生存期(χ2=9.851,P=0.021)有明显关系。结论 NSCLC中AKT2是患者预后不良的生物学标志。