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.     

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.     

小细胞肺癌血清ProGRP（31—98）与神经元性烯醇化酶同步检测的临床价值及其相关性

目的探讨小细胞肺癌（SCLC）患者血清神经元性烯醇化酶（NSE）与ProGRP（31-98）水平同步检测的临床价值及其相关性。方法采用酶联免疫吸附法（ELISA）对159例SCLC患者、97例肺部良性疾病患者、100名健康人进行血中ProGRP（31—98）与NSE水平的检测。结果SCLC治疗前NSE与ProGRP（31—98）的中位值分别为21．33μg／L和323．70pg／ml,肺部良性疾病分别为4．24μg／L和11．94Pg／ml,健康人分别为5．82μg／L和8．54Pg／ml,3组间比较差异均有统计学意义（均P〈0．001）;以NSE10．35ng／L和ProGRP（31-98）47．98Pg／ml为界值,敏感度分别为71．1％和88．7％,特异度分别为95．5％和96．9％,两项联合检测的敏感度和特异度分别为95．6％和96．8％。SCLC局限期和广泛期NSE中位值分别为14．75μg／L和34．10μg／L,敏感度分别为51．14％和93．44％,ProGRP（31—98）中位值分别为143．14Pg／ml和1061．14Pg／ml,敏感度分别为80．61％和98．61％。治疗后缓解和部分缓解的患者两项血清水平较治疗前明显下降,差异有统计学意义（P〈0．001）,未缓解和进展期的患者治疗前后无明显变化。SCLC患者NSE和ProGRP（31-98）血清水平的检测有显著相关性（r=0．379,P〈0．01）。结论NSE和ProGRP（31—98）血清水平有明显的相关性,作为SCLC治疗前诊断和疗效观察均有一定的指导意义,但ProGRP（31．98）,特别是对早期SCLC的诊断有更好的敏感性和准确度,两项联合可进一步提高检测的阳性率和有效性。     

胃泌素释放肽前体在小细胞肺癌诊断及预后的临床价值

胃泌素释放肽前体(ProGRP)作为一种新的小细胞肺癌的肿瘤标志物,双抗体夹心酶联免疫吸附测定(ELISA)方法显示对小细胞肺癌诊断具有较高的敏感性和特异性。相比神经元特异烯醇化酶(NSE)更适宜用于小细胞肺癌的早期诊断。ProGRP在小细胞肺癌治疗与预后监测上也体现了优越性。临床研究发现,肾小球滤过率降低是假阳性的主要因素。临床上联合检测ProGRP和NSE,对小细胞肺癌的早期诊断、监测疗效及预后价值更大。     

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.     

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     

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。     

Cut-off levels of NSE to differentiate SCLC from NSCLC

Neuron-specific enolase (NSE) is a specific tumor marker in small cell lung cancer (SCLC) patients, however, it has been reported that serum NSE levels are elevated in some patients with non-small cell lung cancer (NSCLC). To determine the most suitable cut-off level to distinguish between these two types of cancers, NSE levels were measured on serum samples of 417 patients with lung cancer without clinical information. Receiver operating characteristic (ROC) curve showed 14.5 ng/ml as a cut-off level and the 95 percentile serum NSE level in NSCLC was 20.5 ng/ml. None of the NSCLC patients had serum NSE levels more than 70 ng/ml. The measurement of serum NSE provides a discrimination between NSCLC and SCLC. If an NSCLC patient presents with a NSE level >20.5 ng/ml, pathological features must be examined with regard to the neuroendocrine differentiation.     

检测肿瘤标志物ProGRP、NSE、CYFRA21-1、CEA对胸腔积液鉴别诊断价值的研究

背景与目的 恶性胸腔积液多由肺癌引起，肿瘤标志物检测对其鉴别诊断有一定临床价值。本研究的目的是探讨血清及胸腔积液胃泌素前体释放肽片断31—98（ProGRP）、神经元烯醇化酶（NSE）、细胞角蛋白19（cYFRA21—1）和癌胚抗原（CEA）单项或联合检测对肺癌所致恶性胸腔积液鉴别诊断与组织学分型的临床价值。方法 将肺癌所致的恶性胸腔积液患者按原发肿瘤类型分为小细胞肺癌（SCLC）组、肺腺癌组及肺鳞癌组，同时以良性胸腔积液组、健康对照组作为对照。评估胸腔积液ProGRP、NSE、CYFRA21—1和CEA单项及联合检测对各组恶性胸腔积液的诊断价值。结果 血清及胸腔积液ProGRP、NSE、CYFRA21—1、CEA在各恶性胸腔积液组的水平均明显高于对照组（P〈0．01）。SCLC组检测胸腔积液ProGRP的Youden指数和诊断准确性最高；肺腺癌和肺鳞癌组则以胸腔积液CEA＋CYFRA21—1联合检测（按平行试验）的Youden指数及诊断准确性最高。结论胸腔积液肿瘤标志物系列（ProGRP、NSE、CYFRA21—1、CEA）检查对恶性胸腔积液的鉴别诊断与组织学分型有很大的临床价值。胸腔积液ProGRP为SCLC所致恶性胸腔积液的最佳肿瘤标志物；胸腔积液cEA＋cYFRA21—1联合检测（按平行试验）为肺腺癌、肺鳞癌所致恶性胸腔积液较好的辅助诊断指标。     

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.     

五种肿瘤标志物联检在小细胞肺癌诊断中的价值

目的:探讨五种肿瘤标志物［癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（Cyfra21-1）、胃泌素释放肽前体（ProGRP）、人附睾蛋白4（HE4）］联合检测在不同分期小细胞肺癌诊断中的价值。方法:应用电化学发光法分别检测117例小细胞肺癌患者（Ⅰ期23例、Ⅱ期26例、Ⅲ期39例、Ⅳ期29例）,70例肺部良性疾病患者及120名健康体检者血清中CEA、NSE、Cyfra21-1、ProGRP和HE4水平。结果:小细胞肺癌组五种肿瘤标志物水平均高于健康对照组和肺部良性病变组,差异有统计学意义（P＜0.05）;血清ProGRP浓度随疾病进展而明显升高,其表达水平与临床分期密切相关（P＜0.05）。血清HE4表达水平Ⅱ期高于Ⅰ期,Ⅳ期高于Ⅲ期,差异有统计学意义（P＜0.05）;五种肿瘤标志物联合检测诊断小细胞肺癌的效能最高,各单项指标诊断效能由高到低依次为AUCProGRP 0.91>AUCHE4 0.89>AUCNSE 0.80>AUCCyfra21-1 0.64>AUCCEA 0.60。结论:血清ProGRP是诊断不同分期SCLC良好的肿瘤标志物,在SCLC早期也具有较高的灵敏度和特异度,血清HE4和NSE是较好的补充,多肿瘤标志物联合检测仍是提高诊断效能的最佳选择。     

胃泌素释放肽前体作为小细胞肺癌标记物的临床研究

目的 评价胃泌素释放肽前体(progastrin-releasing peptide，ProGRP)作为小细胞肺癌(SCLC)新标记物的临床意义。方法 回顾性分析经病理证实的55例SCLC初治患者血清中ProGRP水平，并观察其与肿瘤分期、治疗效果的关系。结果 ProGRP诊断SCLC的灵敏度为80．0％，特异度为97．0％；进展期SCLC患者血清ProGRP平均水平显著高于局限期患者，二者分别为820.Ong/L和205.86ng/L(P=0．0003)；临床治疗有效的SCLC患者，治疗后ProGRP水平较治疗前明显下降，而治疗无效病例则无下降甚至升高。结论 ProGRP作为SCLC新的标记物，具有敏感性高、特异性强的特点，并可准确反映SCLC病情及对化疗的反应。     

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。     

Significance of serum pro-gastrin-releasing peptide as a predictor of relapse of small cell lung cancer: comparative evaluation with neuron-specific enolase and carcinoembryonic antigen

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) have been reported to be useful markers for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer (SCLC). Recently, pro-gastrin-releasing peptide (Pro-GRP) became available as a sensitive, specific, and reliable tumor marker for patients with SCLC. The aim of this study is to determine the most useful tumor marker to detect the relapse of SCLC. Furthermore, we analyzed the relationship between tumor markers at relapse and survival from relapse or response to salvage chemotherapy. Medical records were reviewed to obtain serum levels of Pro-GRP, NSE, and CEA before and after the initial chemotherapy, and at relapse. Consecutive 66 patients with SCLC, with an objective response and confirmed relapse treated at the National Cancer Center Hospital East, were analyzed in this study. The percentages of patients whose tumor marker level were elevated before treatment, decreased after the treatment, and increased again at relapse were 67% (95% CI, 55-78) for Pro-GRP, 20% (10-29) for NSE, and 38% (26-50) for CEA. Multivariate analysis indicated that poor performance status before initial treatment and elevated serum levels of lactate dehydrogenase at relapse were poor prognostic factors for patients with recurrent SCLC (P<0.005). None of the serum levels of Pro-GRP, NSE, and CEA at relapse was a significant prognostic factor and associated with an objective response to salvage chemotherapy. The present study demonstrated that serum levels of Pro-GRP reflect the disease course of patients with SCLC most accurately.     

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。     

神经元特异性烯醇化酶对小细胞肺癌诊断的临床价值

目的：探讨血清NSE对小细胞肺癌的诊断,分期及预后的临床价值,以及同时探讨标本溶血程度对NSE浓度的影响。方法：采用ELISA法,检测83例SCLC患者,63例肺良性疾病,62例正常对照及35例溶血标本的NSE水平。结果：SCLC组血清NSE水平（37．64±36．95）μg／L显著高于肺良性疾病组（11．94±4．19）μg／L和正常对照组（8．92±3．95）μg／L（P〈0．01）;SCLCⅢ,Ⅳ期患者血清NSE水平（53．58±40．87）明显高于Ⅰ,Ⅱ期（14．66±6．48）（P〈0．01）。SCLC治疗前NSE水平显著高于治疗后（P〈0．05）。以NSE水平为指标诊断SCLC的敏感性、特异性、准确性,分别为67．3％、83．1％和85．4％。标本溶血对NSE测定影响很大,并且随着溶血程度的增加NSE结果显著升高。结论：NSE可作为较好的小细胞肺癌肿瘤标志物,对SCLC诊断,尤其对临床分期及预后有重要参考价值。血清NSE值随溶血程度呈递增趋势,因此,应严格避免溶血,以减少假阳性的发生。     

联合检测血清胃泌素释放肽前体和特异性组织多肽抗原在小细胞肺癌诊断中的临床价值

目的：探讨联合检测血清胃泌素释放肽前体（ProGRP）和组织多肽特异性抗原（TPS）在小细胞肺癌（SCLC）诊断中的临床意义。方法：采用ELISA法测定93例SCLC患者、63例肺良性疾病患者和62例正常对照组的ProGRP和TPS水平,并对其结果进行比较。结果：SCLC组患者血清ProGRP,TPS水平[（436．4±765．8）ng／ml、（367．8±518．7）U／L]显著高于肺良陆突扁组[（21．7±9．5）ng／ml、（101．1±45．1）U／L]和正常对照组[（17．3±9．5）．g／ml、（85．6±37．4）U／L]（P〈0．01）,SCLC组患者血清ProGRP、TPS水平Ⅲ、Ⅳ期显著高于Ⅰ、Ⅱ期（P〈0．01）,ProGRP和TPS诊断SCLC的敏感性分别为67．5％和59．4％,特异性分别为97．6％和82．4％。Ⅲ、Ⅳ期（79．6％,83．7％）ProGRP和TPS诊断SCLC的敏感性均明显高于Ⅰ、Ⅱ期（50％,52．9％）。联合检测ProGRP和TPS敏感性和特异性分别为81．9％和80％。治疗前ProGRP和TPS水平[（604．4±637．3）ng／ml、（538．3±650．5）U／L]分别是治疗后[（141．5±179．1）ng／ml、（275．2±269．9）U／L]的4．27倍和1．96倍,治疗前ProGRP、TPS和治疗后比较有显著差异（P〈0．05）,治疗效果明显。结论：ProGRP作为一种新的SCLC肿瘤标志物,对SCLC诊断敏感、特异,ProGRP比TPS具有更高的特异性,同时检测,起到优势互补的作用,有助于提高SCLC早期的阳性检出率,减少漏诊率,对判别病情变化及疗效有重要作用。     

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.     

可溶性主要组织相容性复合体Ⅰ类相关分子A与肺癌的相关性

目的探讨可溶性主要组织相容性复合体I类相关分子A（sMICA）对肺癌诊断的临床参考价值，评价肺癌患者血清sMICA表达水平与肿瘤生物学之间的相关性。方法采用酶联免疫吸附法对116例肺癌患者血清sMICA进行检测，并对其中的91例初治患者血清CEA、NSE、CA～199、CYFRA-211、SCC、ProGRP进行检测，与50名健康人血清sMICA作对照。结果肺癌患者血清sMICA显著高于健康人（P〈0．001）；sMICA作为肺癌诊断的-项指标，以240．5ng／L作为截点，其敏感度为90．1％，特异度为46．9％，与上述6项血清肿瘤标志物相比较，阳性检测率较高（P〈0．001）；治疗有效的肺癌患者化疗后sMICA水平下降（P〈0．05），复发转移肺癌患者血清sMICA与初诊患者比较显著升高（P〈0．001）。结论sMICA可作为-项新的肺癌肿瘤标志物，其敏感度、特异度均较高，单项阳性检出率均优于其他6种肿瘤标志物，且sMICA与肺癌的进展、转移有关，监测sMICA有助于观察疗效，评估预后。