Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer

Vascular endothelial growth factor (VEGF) increases microvascular permeability and stimulates endothelial cell growth. p53 Overexpression has been associated with resistance to cisplatin-based chemotherapy in patients (pts) with NSCLC. The aim of this study was to evaluate the predictive role of VEGF for chemotherapy response, its relationship with p53, Rb, Bcl-2 and hemoglobin levels and its impact on overall survival in pts with advanced NSCLC. Bronchial or fine-needle biopsy specimens from 85 pts with NSCLC obtained before chemotherapy were analyzed using an immunohistochemical method for VEGF, p53, Rb and Bcl-2. There were 73 males and 12 females with a median age of 62.6 years. The majority of pts (48%) had squamous cell histology. Ten pts had stage IIIA, 25 stage IIIB and 50 stage IV. Thirty six (43%) pts had positive immunostaining for VEGF, 37 (44%) had positive p53, 53 (62%) had negative Rb and 4 (5%) had positive Bcl-2. VEGF was negatively correlated with Rb (r(s) = 0.26; P = 0.015), positively with Bcl-2 (r(s) = 0.22; P = 0.42), whereas no statistically significant correlation with p53, age, stage and histological type was found. In a logistic regression model, adjusting for treatment, VEGF expression was not associated with chemotherapy response (odds ratio (OR) = 1.01; P = 0.085 ), unlike p53 positivity and Rb negativity ( OR = 4.0, P = 0.005; OR = 2.6, P = 0.016, respectively). A statistically significant higher VEGF expression was detected in the subgroups defined, using as cut-off value Hb median level (13.3g/dl) (chi-square = 5.00; ; one d.f.; P = 0.025). At a median follow-up time of 8.4 years, 2-year survival was 21%. After adjustment for stage and chemotherapy treatment, VEGF expression was not associated with a better overall survival (OR = 1.06; P = 0.80), unlike Bcl-2 positivity showed a statistically significant effect (OR = 0.28; p = 0.02). Our results suggest that VEGF is weakly correlated with regulators of apoptosis and has not been shown to be an independent predictive factor for resistance to cisplatin-based chemotherapy and prognostic for survival.     

Serum levels of intercellular adhesion molecule ICAM-1 and E-selectin in advanced stage non-small cell lung cancer

Cell adhesion is a basic count in inter- and intra-cellular communication and plays an important role in tumor progression. This study was conducted to investigate the serum levels of intercellular adhesion molecule (ICAM-1) and E-selectin in patients with advanced stage non-small cell lung cancer (NSCLC) and the relationships with known prognostic parameters and therapy. These serum factors were measured of 57 NSCLC patients pathologically verified before and after chemotherapy in comparison with 24 healthy controls by using ELISA method. Serum levels of ICAM-1 were increased significantly in NSCLC patients compared with the healthy controls (P = 0.006). However, serum E-selectin levels were not significantly different from healthy control groups (0.643). No statistically significant relationships were found between investigated all serum parameters and various characteristics of patients, and the diseases such as stage and tumor burden. Likewise, we also found no correlation between serum ICAM-1 and E-selectin (P = 0.78). We found that serum ICAM-1 levels were decreased owing to the chemotherapy effect, independently from chemotherapy response. However, serum E-selectin levels were not changed by the chemotherapy effect. The median survival of all patients was 11.9 months and 1-year survival rate was 47.6%. We found that patients performance status (P = 0.013), age (P = 0.015), and weight loss (P = 0.007) were prognostic factors for survival. Serum E-selectin levels showed a trend (P = 0.08) related to worse prognosis, however serum ICAM-1 levels were determined as ineffective on survival (P = 0.11). Multivariate analysis revealed that only weight loss (P = 0.005) and E-selectin levels (P = 0.002) remained as an independent prognostic factor for survival in patients with advanced NSCLC. In conclusion, our data suggest that higher serum ICAM-1 can be useful for diagnosis while E-selectin levels have prognostic significance and could be a potential prognostic factor in NSCLC patients.     

Prognostic factors in advanced non-small cell lung cancer: elevated serum levels of neuron specific enolase indicate poor prognosis

BACKGROUND: Non-small cell lung cancer (NSCLC) is resistant to chemotherapy and prognosis of advanced NSCLC patients is considered to be dependent on various prognostic factors. METHODS: We analyzed prognostic factors in patients with advanced NSCLC who had been enrolled in clinical trials conducted by the Okayama Lung Cancer Study Group between 1978 and 1992 using two kinds of multivariate analysis, Cox's multivariate analysis and recursive partitioning and amalgamation (RPA) analysis. RESULTS: The first analysis was performed on 261 patients using 28 variables. Performance status (PS), clinical stage, liver metastasis or serum albumin level was an independent prognostic factor by Cox's analysis. In the second analysis performed on 128 patients having data on neuron specific enolase (NSE), NSE was the most important prognostic factor. Using the RPA method, three subgroups with significantly different survival potentials were defined. Among them, patients with normal serum NSE levels and good PS were found to obtain a markedly favorable prognosis [median survival time (MST) 22.1 months, 3-year survival rate 42.9%], whereas the survival of patients with elevated serum NSE levels and bone metastasis was extremely short (MST 4.7 months, 3-year survival rate 0%). CONCLUSIONS: These results indicate that analysis of prognostic factors including serum levels of NSE is useful for predicting the survival of patients with advanced NSCLC.     

Circulating angiogenic cytokines in patients with advanced non-small cell lung cancer: correlation with treatment response and survival

Tumor angiogenesis is stimulated by a pro-angiogenic shift in both inducers and inhibitors of endothelial growth. To study this shift, we measured serum and plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin, and thrombospondin 1 (TSP1) in 21 advanced non-small cell lung cancer (NSCLC) patients and 46 healthy control subjects. In addition, we assessed the relevance of these levels to disease outcome. Cytokine levels were prospectively measured in plasma and serum by enzyme-linked immunosorbent assay at three times: before chemotherapy and at 1 and 12 weeks following initiation of chemotherapy. In NSCLC patients, serum VEGF levels (sVEGF) were elevated (p<0.001), whereas serum and plasma TSP1 levels were lower (p=0.012 and p=0.004, respectively) than in healthy control subjects. Pretreatment plasma endostatin and serum bFGF levels were higher in NSCLC patients than in healthy controls (p=0.05 and 0.01, respectively). Change in sVEGF at week 12 after initiation of chemotherapy correlated with response to therapy (p=0.002). Patients with pretreatment sVEGF levels <500 pg/mL had a median survival of 11 months, but those with sVEGF >500 pg/mL had only a 6 months' median survival (p < 0.03). In NSCLC patients, VEGF levels are increased, whereas TSP1 levels are decreased, which may trigger and sustain tumor angiogenesis. High levels of serum VEGF at the time of presentation with NSCLC may predict worse survival.     

Serum vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in small cell lung cancer

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.     

Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.     

Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer.

BACKGROUND: Matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) are two proteins involved in angiogenesis. In the present study we investigated the association of pretreatment MMP-9 and VEGF serum levels with clinicopathological parameters and outcome in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From February 1998 to October 1999, pretreatment serum levels of MMP-9 and VEGF were analysed in 118 patients with enzyme-linked immunoassays. At diagnosis 50 patients (42%) were staged as early disease (I/II), 27 patients (23%) as locally advanced (IIIA/IIIB), and 41 patients (35%) had metastatic disease (IV). In 72 of the 118 patients tumours were resected and 46 patients received combination chemotherapy with gemcitabine and vinorelbine. RESULTS: The median survival of all 118 patients was 602 days. The 72 patients who had undergone surgery had a median survival of 972 days and the 46 patients who were treated with chemotherapy had a median survival of 298 days (P <0.001). Resected patients with stage I/II disease and an MMP-9 serum level 相似文献   

The clinical relevance of Bcl-2, Rb and p53 expression in advanced non-small cell lung cancer

PURPOSE: The aim of this study was to evaluate the impact of Bcl-2, retinoblastoma (Rb) and p53 proteins on overall survival of 102 patients with locally advanced and metastatic NSCLC who underwent cisplatin-based chemotherapy. MATERIALS AND METHODS: Paraffin-embedded bronchial biopsy and fine-needle biopsy specimens were evaluated by an immunostaining method. RESULTS: Median age of analyzed patients was 61 years. Male/female ratio was 88/14. There were 10 (10%) patients with stage IIIA, 37 (36%) with stage IIIB and 55 (54%) with stage IV NSCLC. Only 15 (15%) tumor specimens had no detectable alterations for analyzed factors. Forty-six samples (45%) had positive immunostaining for p53, 61 (60%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for Bcl-2. Median and 5-year survival of analyzed population was 12 months and 6%, respectively. In univariate analysis Bcl-2 overexpression, stage (III versus IV) and normal lactate dehydrogenase (LDH) serum levels were associated with better overall survival (P<0.02, 0.001 and 0.03). In multivariate analysis, only stage was identified as an independent predictive factor. CONCLUSION: High frequency of Rb and Bcl-2 loss was detected in patients with advanced NSCLC. P53, Rb and Bcl-2 have not been shown to be independent predictors of survival even if Bcl-2 might have a particular relevance in patients with advanced NSCLC and should be better explored in this setting.     

Ⅲ期Ⅳ期非小细胞肺癌预后影响因素分析

目的　研究Ⅲ、Ⅳ期非小细胞肺癌 (NSCLC)患者的预后相关因素 ,建立具有临床实用性的预后模型。方法　采用Kaplan Meier和Cox回归方法分析 114例NSCLC患者治疗前血清神经元特异性烯醇化酶 (NSE)、癌胚抗原 (CEA)、Cyfra2 1 1、CA12 5、IL 2、sIL 2R等 6种肿瘤标记物的水平及常规临床因素 ,如年龄、性别、吸烟指数、KPS评分、临床分期等与生存率的关系。结果　单因素分析表明 ,临床分期、KPS评分、性别以及治疗前血清Cyfra2 1 1和CA12 5水平与NSCLC患者生存率有关。多因素分析表明 ,Cyfra2 1 1、临床分期及治疗情况是独立的预后影响因素 ,Cyfra2 1 1>3.5mg/L、临床分期为Ⅳ期、治疗少于 3周期时 ,相对危险性 (RR)分别为 1.6 91,2 .2 2 9和 3.0 35。化疗 3周期及以上的患者 ,Cyfra2 1 1、sIL 2R及临床分期是独立的预后影响因素。建立患者治疗前的预后指数 (PI)模型 :PI =Cyfra2 1 1 sIL 2R Stage。化疗 3周期及以上者 ,PI=0时 ,中位生存期 18个月 ;PI=1或 2时为 8个月 ,PI =3时为 5个月。结论　治疗前血清Cyfra2 1 1、sIL 2R和临床分期 ,是Ⅲ、Ⅳ期NSCLC患者独立的预后影响因素。采用患者治疗前血清Cyfra2 1 1、sIL 2R及临床分期建立的预后指数模型有实际应用价值。     

The prognostic significance of circulating neuroendocrine markers chromogranin a, pro-gastrin-releasing peptide and neuron-specific enolase in patients with advanced non-small-cell lung cancer.

BACKGROUND: Chromogranin A (CGA), Pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) are known as immunohistochemical tissue markers closely associated with neuroendocrine differentiation in non-small-cell lung carcinoma (NSCLC). The aim of the present study was to assess the value of serum levels of these markers in predicting response to chemotherapy and survival of patients with unresectable NSCLC. METHODS: The study included 67 patients with advanced NSCLC treated with chemotherapy. Before treatment, serum levels of CGA, ProGRP and NSE were measured with commercial kits. RESULTS: No association was found between serum NSE and age, gender, histology, performance status or extent of the disease. Distribution of serum CGA differed significantly according to gender and histology, with higher levels being found in men (p = 0.01) and in squamous cell carcinoma (p = 0.01). Serum ProGRP levels correlated with disease extent, being higher in patients with metastatic disease (M1) than in those with locoregional disease (M0; p = 0.02). The association of NSE, CGA and ProGRP levels with response to chemotherapy was not significant. While NSE had no impact on survival, the median survival was shorter for patients with elevated serum CGA and longer for patients with high ProGRP levels. Association with survival was significant when the Classification and Regression Tree (CART)-derived or median cutoff points were explored. On inclusion in multivariate Cox models, both CGA and ProGRP retained significance with high levels showing an opposite effect on survival [CART-derived cutoff points: CGA, relative risk (RR) -4.0; p < 0.001, and ProGRP, RR -0.4; p = 0.006, and median cutoff points: CGA, RR -1.8; p = 0.04, and ProGRP, RR -0.5; p = 0.03]. The combined use of CGA, ProGRP and NSE allowed for definition of two sets of patients with significantly different median survival times (25.2 vs. 8.8 months, p = 0.0001). CONCLUSIONS: In the circulation, CGA and Pro-GRP appear to bear important information related to the prognosis for NSCLC patients before chemotherapy. While a high CGA before treatment was found as an unfavorable prognostic determinant, a high ProGRP conferred a survival advantage. The combined use of serum CGA, ProGRP and NSE may supply additional information to prognosis.     

Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)

PURPOSE: In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. RESULTS: Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level (P=0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. CONCLUSIONS: The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.     

晚期非小细胞肺癌患者血清癌胚抗原变化与预后的关系

目的：探讨晚期非小细胞肺癌（ＮＳＣＬＣ）患者化疗前血清癌胚抗原（ＣＥＡ）基础水平和一线化疗２周期后血清ＣＥＡ的反应性与其预后的关系。方法：回顾分析１０６例晚期ＮＳＣＬＣ患者的临床病理特征和生存资料,采用放射免疫分析法检测患者化疗前及化疗２周期后血清ＣＥＡ的含量,并对检测结果进行统计分析。结果：血清基础ＣＥＡ水平与年龄及ＴＮＭ分期相关,ＣＥＡ的反应性与性别、年龄、病理类型、分期均无明显相关性。Ｋａｐｌａｎ-Ｍｅｉｅｒ生存分析和Ｃｏｘ模型多因素分析,血清基础ＣＥＡ水平、ＣＥＡ反应性与患者预后明显相关,且两者均是影响晚期ＮＳＣＬＣ患者预后的独立危险因素。亚组分析发现：腺癌组血清ＣＥＡ基础水平及ＣＥＡ反应性与预后存在明显相关性,而鳞癌组无明显相关性。结论：对于晚期ＮＳＣＬＣ患者尤其是腺癌患者,血清ＣＥＡ基础水平及化疗后血清ＣＥＡ的反应性可以作为判断ＮＳＣＬＣ预后的参考指标。     

非小细胞肺癌血清VEGF与CA125 CEA Cyfra21-1 的相关性及临床意义*

目的:探讨化疗前血清血管内皮生长因子（VEGF）检测在非小细胞肺癌（NSCLC ）中的临床应用价值,同时测定血清中CA125、CEA 、Cyfra21-1 的滴度及其相关性。方法:采用抗人VEGF单克隆抗体、夹心ELISA 法测定78例NSCLC 患者血清VEGF浓度。同时利用放射免疫法检测血清中CEA 、CA125、Cyfra21-1 的浓度。结果:NSCLC 有远处转移组血清VEGF、CA125、CEA 浓度显著高于无远处转移组（P<0.05）;有淋巴结转移组血清VEGF显著高于无淋巴结转移组（P<0.05）。 血清VEGF和CA125、CEA 在Ⅲ+ Ⅳ期NSCLC 的表达显著高于I+II 期NSCLC（P<0.05）。 血清CEA 在腺癌中显著增高（P<0.05）。 血清VEGF、CA125 阴性组的化疗有效率（35.3% 、35.7%）显著高于阳性组（7.7% 、15.8%）（P=0.004,0.006）。 化疗前血清CEA 阴性者的中位总生存时间（mOS ）较阳性者明显延长（分别为36个月,20个月;P=0.04）;而血清VEGF、Cyfra21-1、CA125 浓度对mOS 无明显影响（P 值分别为0.07,0.099,0.19）。 血清CEA 、VEGF、Cyfra21-1、CA125 表达对中位无瘤生存期（mTTP）均无明显影响（P 值分别为0.119,0.280,0.146,0.230）。 NSCLC 患者血清VEGF 与CEA 表达存在显著正相关（P<0.05）,其他肿瘤标志物之间无显著相关性（P>0.05）。 结论:综合检测NSCLC 患者化疗前血清肿瘤标志物可能有利于协助诊断、预测转移、评价化疗疗效及判断预后。      

Ⅳ期非小细胞肺癌预后因素分析

目的:回顾分析Ⅳ期非小细胞肺癌患者(NSCLC)的预后因素,指导临床个体规范化的治疗。方法:采用Kaplan Meier生存分析以及COX回归模型分析57例Ⅳ期初治NSCLC患者临床特征,如年龄、性别、吸烟指数、病理类型以及治疗前血浆中CEA和Cyfra21-1的水平等以及治疗相关因素与生存率的关系,筛选Ⅳ期NSCLC患者预后相关因素。结果:单因素分析表明,患者的年龄、吸烟指数、KPS评分、治疗前血浆Cyfra21-1水平以及化疗与否、化疗周期数与Ⅳ期NSCLC患者的生存率有关。多因素分析表明,Cyfra21-1、KPS评分、化疗周期是独立的预后因素。结论:治疗前血浆中Cyfra21-1的水平,KPS评分以及化疗周期数为Ⅳ期NSCLC患者的独立预后因素。无化疗禁忌症的Ⅳ期NSCLC患者积极规范合理的治疗能延长患者生存期,具有重要的临床意义。     

The value of serum Bcl-2 levels in advanced lung cancer patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.     

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer

BACKGROUND: The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS: One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (> or =20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS: CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC.     

NSCLC患者血清Ang2与VEGF动态变化的关系

目的 探讨非小细胞肺癌（NSCLC）患者病程中血管生成素2（Ang2）和血管内皮生长因子（VEGF）的变化情况,评价在肿瘤发生、进展、预后的临床意义。方法 对82例首诊未经治疗的NSCLC患者行ELISA法定量检测外周血Ang2与VEGF水平。结果 NSCLC患者外周血Ang2与VEGF水平较对照组明显升高［Ang2：（1326.8±942.9）pg/ml vs. （445.0±213.0） pg/ml, P<0.01;VEGF：（846.8±459.6）pg/ml vs. （691.3±369.6） pg/ml, P<0.05］。Ang2在早期NSCLC开始明显升高,但在各进展期之间比较差异无统计学意义,进入晚期后在越接近死亡的患者Ang2又再有上升趋势。VEGF在早期未见升高,进入进展期后逐渐升高,在未有远处转移的患者,原发灶直径越大,VEGF越高。COX回归分析显示临床分期与VEGF是NSCLC生存预后的独立危险因素(P<0.05）。结论 NSCLC患者血清Ang2与 VEGF均明显升高, 对早期NSCLC患者检测血清Ang2较VEGF有更好的辅助诊断价值,在NSCLC进展期检测血清VEGF较Ang2更有助于评价肿瘤进展情况,在NSCLC晚期检测血清Ang2升高较VEGF更能提示临终期。     

晚期非小细胞肺癌患者血清载脂蛋白A-I水平及其临床意义分析

目的 探讨血清载脂蛋白A-I（ApoA-I）与晚期非小细胞肺癌（NSCLC）患者临床病理特征的关系及其对患者预后的影响。方法 回顾性分析2009年1月至2014年12月第二军医大学附属长海医院经病理组织学诊断的117例ⅢB～Ⅳ期NSCLC患者的临床资料,以治疗前ApoA-I基线值的中位数为截点分为高、低两组,分析ApoA-I水平与患者临床病理特征的关系,单因素及多因素生存分析评价ApoA-I对预后的影响。结果 低于治疗前ApoA-I基线值组（≤1.2 g／L）为50例（42.7％）,高于治疗前ApoA-I基线值组（＞1.2 g／L）为67例（57.3％）;治疗前ApoA-I基线值与肿瘤直径、TNM分期、治疗前C反应蛋白值、血白蛋白及ECOG PS评分均有关（P＜0.05）。低于治疗前ApoA-I基线值组和高于治疗前ApoA-I基线值组患者的中位生存期（OS）分别为10.1个月和15.1个月,差异有统计学意义（P＜0.05）。单因素分析显示,吸烟指数、治疗前C反应蛋白值、血白蛋白、临床分期、淋巴结转移、ECOG PS评分及治疗前ApoA-I基线值均为影响患者预后的因素。Cox回归多因素分析显示,治疗前C反应蛋白值、临床分期、 ECOG PS评分及治疗前ApoA-I基线值为影响患者预后的独立危险因素。结论 血清ApoA-I水平低提示晚期NSCLC患者预后不良,ApoA-I可能是晚期NSCLC潜在的生物学标志物。     

晚期非小细胞肺癌患者外周血VEGF和bFGF及MMP-9水平与预后的关系

目的 检测晚期非小细胞肺癌（NSCLC）患者化疗前后外周血血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和基质金属蛋白酶-9（MMP-9）的水平,探讨其与疗效、预后的关系。方法 酶联免疫吸附试验（ELISA）检测46例晚期NSCLC患者化疗前后血浆VEGF、bFGF和MMP-9水平,并对随访资料进行生存分析,应用COX回归模型分析预后影响因素。结果 化疗前血浆VEGF、bFGF和MMP-9中位值分别为275pg／ml、69pg／ml和122ng／ml,均高于健康对照组（P〈0．05）。化疗前血浆VEGF与bFGF水平正相关,Spearman’S相关系数为0．329。化疗前血浆VEGF、bFGF和MMP-9水平与白细胞、血色素、血小板计数无相关性,与年龄、性别、病理类型、分化程度、TNM分期等亦无关。Ⅳ期广泛转移者（包括骨转移）化疗前血浆MMP-9水平显著高于仅有骨转移者（P=0．013）。化疗后血浆bFGF下降为预后的独立保护因素,RR=11．737（P=0．02）。结论 检测晚期NSCLC患者外周血的某些血管生成相关因子,可能有利于协助预测转移倾向及评价预后。     

Ⅰ期非小细胞肺癌预后因素的研究

目的 探讨Ⅰ期非小细胞肺癌(NSCLC)的联合预后因素。方法 回顾性分析58例Ⅰ期NSCLC患者的临床资料、术后病理结果和免疫组化技术检测的9项基因表达指标(c-myc、MDM2、c-erbB-2、EGFR、p53、p14^ARF、p16^INK4、p21^WAF1、nm23)。观察患者的总生存率、局部区域性复发率和远处转移率。结果 全组5年生存率、局部区域性复发率和远处转移率分别为71．1％,11．1％和33．5％。单因素分析结果表明,肿瘤细胞的低分化是影响总生存率的不良预后因素(P=0.028);c—myc与c-erbB-2的高表达均为影响总生存率和远处转移率的不良预后因素;促进肿瘤增殖基因总分组的高分值(P=0．041)与综合肿瘤基因组的高分值(P=0．006),是总生存率的不良预后因素。多因素分析结果表明,肿瘤细胞的分化程度与综合肿瘤基因的联合表达,是影响总生存率的独立预后因素。本组结果还显示,已行化疗的高危组患者,其总生存率与无远处转移率均优于未行化疗者,但差异尚未见有显著性。结论 肿瘤细胞的分化程度与综合肿瘤基因的表达,可能是Ⅰ期NSCLC的预后因素。高危组患者进行术后化疗似有提高疗效的趋势。