肺癌患者血清ProGRP、CA125、CYFRA21-1和TPS检测的临床意义

目的：探讨血清肿瘤标志物ProGRP、CA125、CYFRA21-1和TPS在肺癌诊断中的价值。方法：回顾性分析180例患者的临床资料和肿瘤标志物水平,评价肿瘤标志物与肺癌的关系。结果：肺癌组患者ProGRP、CA125、CYFRA21-1和TPS阳性率明显高于肺部良性病变组,三项或四项联合检测敏感性和特异性明显优于单项检测。结论：ProGRP、CA125、CYFRA21-1和TPS中至少三项联合检测可提高肺癌诊断的敏感性和特异性。     

Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses

The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer.     

肿瘤标志物和肺门淋巴结与肺腺癌全身骨显像骨转移的关系

 目的 探讨肺腺癌肿瘤标志物与骨转移之间的关系。方法 回顾性分析278例肺腺癌患者的全身骨显像，采用单因素Pearson卡方分析和Logistic二分类回归法对肺腺癌骨转移的相关因素进行分析。结果 （1）单因素卡方分析结果: CA125（P=0.000）、CYFRA21-1（P=0.000）、NSE（P=0.000）、SCC（P=0.036）、CEA（P=0.000）、ALP（P=0.000）、肺门淋巴节（P=0.000）均是骨转移的危险因素（均P<0.05）；（2）二分类分析结果：CA125（P=0.009, OR=1.007）、NSE（P=0.012, OR=1.097）、ALP（P=0.001, OR=1.022）、CEA（P=0.013, OR=1.004）、肺门淋巴节（P=0.029, OR=2.136）是骨转移的危险因素（均P<0.05, 均OR>1），具有统计学意义; SCC（P=0.169, OR=1.194)、ProGRP（P=0.703, OR=1.004）是骨转移的危险因素（均OR>1），但不具统计学意义（均P>0.05）。结论 CA125、NSE、ALP、CEA、肺门淋巴节与骨转移有关；SCC、ProGRP是骨转移的危险因素，但不具统计学意义；CYFRA21-1与骨转移无关。     

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。     

Primary small cell carcinoma of the esophagus with achalasia in a patient in whom pro-gastrin-releasing peptide and neuron-specific enolase levels reflected the clinical course during chemotherapy

We report a case of primary small cell carcinoma of the esophagus in a patient with achalasia in whom pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) levels were measured. Although chemotherapy markedly reduced the size of the primary tumor and lymph node metastases, it had no effect on liver metastases. The tumor marker levels decreased after chemotherapy as the primary tumor and lymph node metastases decreased in size, and they increased as the liver metastases enlarged. However, there was a discrepancy between the levels of ProGRP and NSE during the patient's clinical course. We demonstrate the usfulness of measuring ProGRP and NSE levels to assess the effect of chemotherapy in patients with esophageal small cell carcinoma. Received: April 30, 1998/Accepted: November 27, 1998     

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。     

Usefulness of pro-gastrin-releasing peptide as a predictor of the incidence of brain metastasis and effect of prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan–Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.     

CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients

Abstract Serum levels of CYFRA 21-1(cytokeratin-19 fragment) and ProGRP (pro-gastrin-releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme-linked immunoadsorbent assay) in 27 (for CYFRA 21-1; male 13, female 14; age 54 ± 17 years) or 22 (for ProGRP; male 9, female 13; age 59 ± 18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59 ± 14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48 ± 9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21-1 and ProGRP levels. Serum levels of CYFRA 21-1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07 ± 1.56 ng/mL) and in 73% of CAPD patients (mean 4.87 ± 1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0 ± 59.4 pg/mL) and in 93% of CAPD patients (mean 112.4 ± 4.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.     

Preliminary radioimmunoimaging and biodistribution of 131iodine-labeled single-chain antibody fragment against progastrin-releasing peptide(31–98) in small cell lung cancer xenografts

Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.     

国产和进口化学发光免疫分析系统检测血清ProGRP的比对分析

目的 探讨国产自主研发AE-180全自动化学发光免疫分析系统和进口的罗氏cobas e 601电化学发光免疫分析系统同时检测血清ProGRP结果的可比性.方法 依据美国国家临床实验室标准化协会(NCCLS)指南文件EP9-A2[1]文件要求,以罗氏cobas e 601电化学发光免疫分析仪为对比仪器,苏州长光华医自主研发的AE-180全自动化学发光免疫分析仪为实验仪器,采用患者血清样本检测胃泌素释放肽前体(ProGRP)含量,通过实验数据的比对分析,对两套分析系统之间的偏倚进行评估.结果 在ProGRP测定的线性范围内,两套系统相关性好,r=0.997,直线回归方程为Y=0.9944X+0.5892,在ProGRP医学决定水平处的偏倚可接受.结论 两套系统检测ProGRP结果具有较好的一致性,国产自主研发的AE-180全自动化学发光免疫分析系统检测检测血清ProGRP能够满足临床需要,适于临床实验室推广使用.