Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC)

In this study, we evaluated the clinical usefulness of ProGRP and NSE for diagnosis and prognosis of small-cell lung cancer (SCLC). Serum levels of ProGRP and NSE were determined in 108 healthy subjects, 103 patients with benign pulmonary diseases, 142 with non-small cell lung cancer (NSCLC), and 114 with SCLC. Sensitivity of ProGRP in diagnosis of SCLC was significantly higher than that of NSE (64.9 vs. 43.0%, P < 0.001). The difference was substantial in patients with limited disease (56.5 vs. 20.3%, P < 0.001). However, 11 of 40 SCLC patients with normal levels of serum ProGRP (27.5%) showed elevated levels of serum NSE. In the SCLC patients receiving chemotherapy, the CR rate in patients with elevated NSE levels was significantly lower than in patients with normal levels of NSE (18.5 vs. 61.7%, P < 0.001). Elevation of both ProGRP and NSE was a poor prognostic factor, and patients with elevated levels of either ProGRP or NSE showed shorter survival than those without. From multivariate analysis, NSE was found to have a greater effect on survival of SCLC patients than ProGRP. These findings indicate that ProGRP is more sensitive than NSE for diagnosis of SCLC, while NSE is superior to ProGRP as a prognostic factor. In conclusion, both ProGRP and NSE are useful tumor markers and they have a complementary role for each other in diagnosis and prognosis of SCLC.     

Pro-gastrin-releasing peptide, neuron specific enolase and chromogranin A as serum markers of small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) yields neuroendocrine properties. Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE) and chromogranin A (CGA) are therefore putative serum markers in this disease. AIM: To assess any difference in the sensitivity-specificity relationship between these neuroendocrine markers regarding various control populations and disease extent. METHOD: A total of 146 patients were prospectively assessed clinically and biologically. Serum marker titrations were performed using commercial immunoradiometric assays (NSE, CGA) or ELISA (ProGRP). Areas under receiver operating characteristic curves (AUC-ROC) were calculated in order to assess the sensitivity-specificity relationship of each marker and to compare marker accuracy. Maximum Youden indices were used to determine marker thresholds able to produce the best overall diagnostic information. RESULTS: Assessing the sensitivity in the SCLC population and the specificity in benign lung disease, ProGRP demonstrated the best sensitivity relationship in as much as its AUC-ROC was significantly greater than the ones calculated using NSE and CGA (respective values, 0.95, 0.89, 0.70; two-tailed Z-test <0.05). The ProGRP threshold value, which offered the best sensitivity-specificity relationship was 53 pg/ml corresponding to a 0.80 sensitivity and a 0.96 specificity. In addition, when specificity was assessed in NSCLC and again the sensitivity in the whole SCLC population, ProGRP continued to demonstrate a greater AUC-ROC in comparison with other markers. Using the 53 pg/ml threshold the specificity of this marker was excellent with no false positives in NSCLC. On the other hand, none of the markers were able to discriminate limited from extensive SCLC as suggested by the fact that AUC-ROC, constructed when sensitivity was defined as a positive test in extensive disease and specificity as a true negative test in limited disease, did not reach the upper left octant (AUC 0.65, 0.71 and 0.63 for ProGRP, NSE and CGA, respectively). CONCLUSION: ProGRP yields the best sensitivity-specificity feature in SCLC, a result deserving further studies designed to evaluate the clinical applicability of this marker.     

Pro-gastrin-releasing peptide (31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of ''receiver operator characteristics'' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.     

Are levels of pro-gastrin-releasing peptide or neuron-specific enolase at relapse prognostic factors after relapse in patients with small-cell lung cancer?

The purposes of this study were to assess the relationship of serum levels of pro-gastrin-releasing protein (ProGRP) and neuron-specific enolase (NSE) at relapse with survival after relapse and the response to salvage therapy and to assess whether serum levels of ProGRP and NSE at relapse are useful markers for detecting relapse earlier than are symptoms or radiographic findings in patients with small-cell lung cancer (SCLC). The subjects of this study were 103 patients with SCLC who had achieved a complete response (CR) or partial response (PR) to first-line chemotherapy. We retrospectively evaluated whether ProGRP or NSE increased earlier than symptoms or radiographic findings appeared, and the association between response to salvage therapy and levels of ProGRP or NSE at relapse. In addition, we evaluated the association between survival after relapse and clinical and demographic factors at relapse, including age, sex, response to first-line treatment, sensitivity to first-line treatment, stage, performance status (PS), and serum levels of ProGRP, NSE, and lactate dehydrogenase. At relapse, 69.3% of patients had elevated serum levels of ProGRP, 60.2% had elevated serum levels of NSE, and 81.3% had elevated serum levels of either ProGRP or NSE. However, almost all asymptomatic relapses were detected with radiographic studies. The rate of CR to salvage chemotherapy was significantly lower in patients with elevated levels of NSE (2.2%) than in patients without (26.7%; p = 0.001). Univariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, stage, and PS at relapse were prognostic factors for survival after relapse. Multivariate analysis showed that sensitivity to first-line treatment, serum levels of NSE, and PS at relapse were independent prognostic factors after relapse. In conclusion, serum levels of ProGRP and NSE at relapse are not useful markers for detecting relapse earlier than are symptoms or radiographic findings. On the other hand, the serum level of NSE at relapse is a useful predictive marker for CR to salvage chemotherapy and a useful prognostic factor after relapse in patients with SCLC who have achieved a CR or PR to first-line chemotherapy.     

胃泌素释放肽前体片段31-98检测对小细胞肺癌的临床意义

目的 与神经元特异性烯醇化酶（ＮＳＥ）对照,探讨胃泌素释放肽前体片段３１－９８（ＰｒｏＧＲＰ３１－９８）检测对小细胞肺癌（ＳＣＬＣ）的临床意义。方法 采用ＥＬＩＳＡ检测３０例ＳＣＬＣ、３０例非小细胞肺癌、１５例肺良性疾病、１５例正常健康者和１０例治疗后ＳＣＬＣ患者血液ＰｒｏＧＲＰ３１－９８和ＮＳＥ值．采用ＲＯＣ曲线确定阈值,比较诊断准确性。结果 ＳＣＬＣ组血清ＰｒｏＧＲＰ３１－９８值显著高于对照组     

血清NSE、ProGRP和LDH在小细胞肺癌诊断治疗中的作用

背景与目的小细胞肺癌（small cell lung cancer, SCLC）是一种生长迅速、具有神经内分泌特性的肿瘤。血清神经元特异性烯醇化酶（neuron specific enolase, NSE）、胃泌素释放肽前体（pro-gastrin-releasing peptide, ProGRP）和乳酸脱氢酶（lactic dehydrogenase, LDH）已在SCLC的诊断和治疗中起到一定的辅助作用,本研究旨在通过治疗前后SCLC患者NSE、ProGRP和LDH的变化探讨标志物在肿瘤分期、疗效评价及预测复发方面的价值。方法纳入中国医学科学院肿瘤医院的SCLC初治病例,回顾性分析其临床数据,包括临床特征、治疗前及2周期化疗后的血清NSE、ProGRP及LDH,疗效及无进展生存期。结果治疗前,广泛期（extensive disease, ED）患者NSE、ProGRP及LDH均高于局限期（limited disease, LD）（P<0.005）;LD患者的NSE水平随淋巴结分期的升高而明显增加（P=0.010）;有体重下降的患者NSE及LDH均高于无体重下降者（P=0.032, P=0.014）。化疗2周期后,有效患者的NSE及ProGRP下降程度明显高于疗效为稳定或无效的患者（P=0.015, P=0.002）。LD组化疗周期数>4个及治疗后ProGRP下降明显的患者较化疗周期数≤4个及ProGRP下降不明显的患者复发风险低;而远处转移数目≤2个、疗前LDH正常及治疗后ProGRP的明显下降,提示ED患者的近期复发风险低。此外,肿瘤复发类型（敏感复发、耐药复发、难治复发）与化疗后ProGRP下降程度呈负相关（P=0.044）。多因素分析结果提示治疗周期数是LD组SCLC近期复发的独立影响因素,远处转移数目及治疗后ProGRP的下降程度是ED组SCLC近期复发的独立影响因素。结论血清肿瘤标志物升高的程度与肿瘤负荷相关,ProGRP在治疗后的下降程度可能预测疗效及复发风险。     

Cross-Sectional Study to Establish the Utility of Serum Tumor Markers in the Diagnosis of Lung Cancer

Background: Reliable blood markers for aiding lung cancer (LC) diagnosis and differentiating LC from tuberculosis are lacking in India. Methodology: In this single-centre, cross-sectional, real-world study, serum levels of 5 TMs (CEA, CYFRA 21-1, SCC, ProGRP, NSE) were measured from consented patients with suspicious lung nodules who were candidates for biopsy, and also from healthy controls. TM level measurement was done through electrochemiluminescent immunoassay, followed by histological diagnosis on the biopsied specimen. Using package insert cut-offs, sensitivity and specificity of the 5 TMs were evaluated individually and in combination. Using receiver operating characteristic (ROC) curves of individual TMs, the ability of CEA, CYFRA 21-1, and ProGRP taken together was evaluated for its ability to differentiate LC from no-LC. Results: Out of 178 subjects, 160 had LC (147 NSCLC; 13 SCLC). NSCLC patients had higher median values of CYFRA 21-1 and SCC; SCLC patients had higher median values of CEA, NSE, and ProGRP. Adenocarcinoma-NSCLC patients had higher median values of CEA, CYFRA 21-1, NSE, and ProGRP; squamous-NSCLC patients had higher median value of SCC. For differentiating LC from no-LC, the combination of all 5 TMs (sensitivity:97.5%, specificity:33.3%) and combination of CEA, CYFRA 21-1 and ProGRP (sensitivity:91.3%, specificity:88.9%) were found suitable. Conclusion: Combination of all 5 TMs, and combination of CEA, CYFRA 21-1, and ProGRP represents an easy and non-invasive method for aid in LC diagnosis that does not require technical expertise. TM evaluation can also supplement histological diagnosis of LC.     

ProGRP、NSE单项及联合检测对恶性胸腔积液的诊断价值

目的 探讨血清和胸腔积液胃泌素前体释放肽片断31-98（ProGRP）、神经原烯醇化酶（NSE）单项及联合检测对小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）所致的恶性胸腔积液的诊断价值。方法 采用酶联免疫吸附实验检测36例SCLC（SCLC组）、37例NSCLC（非SCLC组）、36例良性胸腔积液患者（良性胸腔积液组）及35例健康对照者（健康对照组）血清和胸腔积液ProGRP、NSE水平。比较血清和胸腔积液ProGRP、NSE单项及联合检测对恶性胸腔积液的诊断价值。结果 SCLC组、NSCLC组血清和胸腔积液ProGRP、NSE水平均明显高于良性胸腔积液组及健康对照组（P〈0．01）；SCLC组血清及胸腔积液ProGRP、NSE水平均明显高于NSCLC组（P〈0。01）。SCLC组、NSCLC组、良性胸腔积液组及健康对照组的血清ProGRP阳性率分别为83.33％、8.11％、8.33％和2.86％，血清NSE的阳性率分别为72.22％、27.03％、22.22％和17.14％；SCLC组、NSCLC组和良性胸腔积液组胸腔积液ProGRP的阳性率分别为91。67％、2．70％和2.78％，胸腔积液NSE的阳性率分别为80.56％、21.62％和13.89％。血清ProGRP单项检测、NSE单项检测、ProGRP＋NSE联合检测（按序列实验）和ProGRP＋NSE联合检测（按平行实验）诊断SCLC所致的恶性胸腔积液的敏感度分别为0.8333、0.7222、0.7576和0.9167，特异度分别为0.9722、0．8611、1．0000和0．9167，Youden指数分别为0．8056、0.5833、0．7576和0．8333；胸腔积液ProGRP单项检测、NSE单项检测、ProGRP＋NSE联合检测（按序列实验）和ProGRP＋NSE联合检测（按平行实验）诊断SCLC所致的恶性胸腔积液的敏感度分别为0.9167、0.8056、0．8056及0.9444，特异度分别为1．0000、0.8889、1．0000及0．8889，Youden指数分别为0．9167、0．6944、0．8056及0．8333。对血清、胸腔积液ProGRP和NSE水平的检测，无论是单项或是联合检测，诊断NSCLC所致的恶性胸腔积液的敏感度、特异度及Youden指数均较低。结论 血清、胸腔积液ProGRP和NSE检测对SCLC所致的恶性胸腔积液均有一定的辅助诊断价值；胸腔积液ProGRP、NSE检测优于血清检测；ProGRP检测优于NSE检测；胸腔积液ProGRP单项检测对SCLC所致的恶性胸腔积液的鉴别诊断价值最高，其次为ProGRP＋NSE联合检测（按平行实验）；血清、胸腔积液ProGRP和NSE无论单项检测或是联合检测，对NSCLC所致的恶性胸腔积液均无诊断价值。     

Serum vascular endothelial growth factor (VEGF) and bcl-2 levels in advanced stage non-small cell lung cancer

The characteristic changes in cancer process are assumed to be genetic alterations about the imbalance of cell proliferation and apoptotic cell death. This study was conducted to determine the value of the circulating vascular endothelial growth factor (VEGF) and Bcl-2 in patients with advanced stage non-small cell lung cancer (NSCLC). These serum factors were measured of 52 NSCLC patients pathologically verified on before and after chemotherapy in comparison with 16 healthy controls by using ELISA method. Both of the serum levels of VEGF (p = 0.015) and Bcl-2 (p < 0.001) were increased significantly in NSCLC patients compared with the healthy controls. No statistically significant relationships between investigated elevated serum parameters and various characteristics of patients and disease such as stage and tumor burden were determined. Likewise, we also found no correlation between serum VEGF and Bcl-2. Cytotoxic therapy of patients was accompanied by unchanged serum levels of serum factors. The median survival of all patients was 27 weeks and one-year survival rate was 22.4 percent. With the median serum levels as the cut-off value, patients were divided into high- and low-serum parameter groups. While we found that patients' performance status (p < 0.0001), serum LDH level (p = 0.0002), response to chemotherapy (p = 0.0023), and stage of the disease (p = 0.0085) were prognostic factors for survival, serum VEGF (p = 0.48) and Bcl-2 (p = 0.91) levels were determined as ineffective on survival in patients with advanced NSCLC. In conclusion, our data suggest that these serum factors, VEGF and Bcl-2, are useful diagnostic factors, not predictive and prognostic markers for overall survival in advanced NSCLC patients.     

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。     

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.     

血清细胞角蛋白19片段与晚期非小细胞肺癌患者化疗疗效及预后关系的研究

目的:探讨晚期非小细胞肺癌(NSCLC)患者化疗前后血清细胞角蛋白19片段(CYFRA21-1)变化水平与影像学疗效哪个因素与预后的关系最密切。方法:采用电化学发光免疫法检测112例晚期NSCLC患者化疗前后血清CYFRA21-1水平变化,并将其变化水平与临床反应类型进行比较。结果:经过2个周期化疗后,112例患者中有80例可行影像学和血清学疗效评价,其中,影像学客观缓解率为26.3%,疾病控制率为65.0%。80例患者的中位生存期(MST)为9.9个月。影像学缓解(OR)与疾病控制(DC)患者的MST相似(P=0.094),但均长于PD患者(P均<0.001)。化疗后血清CYFRA21-1水平下降幅度与临床疗效相符。血清CYFRA21-1水平下降幅度≥30%和≥60%对于诊断DC和OR有最佳灵敏度和特异度。血清CY-FRA21-1水平下降幅度≥30%与DC(P<0.001)及生存期(P<0.001)密切相关。多因素分析表明,DC(RR=0.450,P=0.017)及血清CYFRA21-1水平下降幅度≥30%(RR=0.429,P=0.002)是影响预后的独立因素,而OR与生存期无关。结论:DC较OR更适合作为判定NSCLC化疗疗效的指标,血清CYFRA21-1水平下降幅度≥30%有望成为评价NSCLC化疗疗效的替代指标。     

局限期小细胞肺癌不同治疗手段疗效与胃泌素释放肽前体及神经元特异性烯醇化酶水平的相关性研究

 目的　探讨不同治疗手段的局限期小细胞肺癌（SCLC）患者分别进行治疗前后血清胃泌素释放肽前体（ProGRP）和神经元特异性烯醇化酶（NSE）水平变化,并评价治疗效果与标志物血清水平的相关性。方法　将150例局限期SCLC患者随机分为3个治疗组,即同步放化疗组、序贯放化疗组、单纯化疗组;应用酶联免疫吸附试验（ELISA）、电化学发光法对3组患者治疗前后ProGRP和NSE水平进行联合检测,并进行数据整理和分析。随访期为1年。结果　3组患者ProGRP及NSE在治疗结束后均明显下降;其ProGRP与NSE的下降幅度依次为同步放化疗组、序贯放化疗组、单纯化疗组（318.96、250.77、226.18 pg／ml及31.72、23.95、17.89 μg／L）;三组按近期疗效好排序,依次为同步放化疗组、序贯放化疗组、单纯化疗组;同步放化疗组明显优于单纯化疗组,差异有统计学意义（P＜0.05）。在各组中,治疗有效的患者ProGRP与NSE的下降幅度明显大于治疗无效的患者;病情进展时,相应ProGRP与NSE上升,差异有统计学意义（P＜0.05）。结论　ProGRP和NSE水平可反映出局限期SCLC患者的病情变化并可评估疗效;同步放化疗优于序贯放化疗和单纯化疗。     

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.     

血清中NSE水平在晚期NSCLC化疗中的临床意义

目的：探讨治疗前血清中神经特异性烯醇化酶(NSE)水平对晚期非小细胞肺癌(NSCLC)近期化疗疗效及远期生存率的影响。方法：用放射免疫法检测145例NSCLC治疗前血清中NSE水平，评价3周期化疗后的疗效，随访生存率。结果：NSE阳性组其近期化疗有效率高(60．1％)，疗效持续时间短(2．0个月)，1年生存率低(15．3％)，NSE阴性组其近期化疗有效率低(40．7％)．疗效持续时间长(5．9个月)，1年生存率高(40．7％)。结论：血清NSE水平可作为预测晚期NSCLC患者预后的有效指标之一。     

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   

组织多肽抗原联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊治中的价值

目的 评估组织多肽抗原（TPA）联合ProGRP、CEA、NSE、SCC、CYFRA21-1在肺癌诊断与疗效监测中的应用价值。方法 用化学发光法和电化学发光法检测238例肺癌患者、25例肺部良性疾病患者及65名健康对照者血清中的TPA、ProGRP、NSE、SCC、CYFRA21-1和CEA水平,并对33例肺癌患者进行随访检测。同时用SPSS19.0统计软件及接受器工作性能曲线（ROC）分析,评价肿瘤标志物的临床应用价值。结果 肺癌患者血清TPA水平（中位数为130.45 U/L）明显高于肺部良性疾病患者（中位数为82.21 U/L）和健康对照组（中位数为70.96 U/L）（P=0.000, 0.002）。根据ROC曲线分析,TPA检测肺癌的临界值为130 U/L,敏感度为50%,特异性为88.9%,相比于其他肺癌标志物( ProGRP、NSE、SCC、CYFRA21-1、CEA）,敏感度较高,特异性稍低。肺癌患者血清TPA水平及阳性率随着肿瘤分期的升高而升高（P均<0.05）。TPA水平与疗效也密切相关,临床治疗有效时TPA下降,而病情恶化或出现转移时则升高。各种组合检测中,以六项组合诊断肺癌的敏感度和有效性最高。结论 TPA联合ProGRP、CEA、NSE、SCC、CYFRA21-1测定在肺癌的诊断、疗效及监测复发转移中,具有一定的临床价值。     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

Pro-gastrin-releasing peptide in patients with benign and malignant diseases.

The specificity and sensitivity of pro-gastrin-releasing peptide (ProGRP) was evaluated in 37 healthy subjects, 197 patients with benign diseases and 310 patients with malignant diseases of different origins. Abnormal ProGRP serum levels (>50 pg/ml) were found in 10% of the patients with benign diseases and in 26.1% of the patients with active cancer. None of the healthy subjects had abnormal ProGRP levels. The benign disease with the highest ProGRP concentration was renal failure, with abnormal values in 51.6% of the patients studied. Excluding patients with renal failure or patients with creatinine levels greater than 1.5 mg/dl, raised ProGRP values (<80 ng/ml) were found in 2.5% (4/160) of patients with benign diseases and in 4.9% of patients with active malignancies other than lung cancer or neuroendocrine tumors (<110 ng/ml). Abnormal ProGRP serum levels were found in 26.2% of patients with non-small cell lung cancer (NSCLC) (mean 40.5 +/- 35.4 pg/ml) and in 76.8% of patients with small cell lung cancer (SCLC) (mean 694 +/- 1,776 pg/ml) (p < 0.001). ProGRP serum levels >300 pg/ml were only found in SCLC patients (41.4%). ProGRP results were related to tumor extension in SCLC (sensitivity in limited disease 58.3%, in extensive disease 95.5%) but not in NSCLC. In summary, renal failure is the most frequent source of false-positive results with ProGRP, and this marker is useful in the histological differential diagnosis of lung cancer.