Serum NSE, CEA, CT, CA 15-3 levels in human lung cancer

The significance of neuron specific enolase (NSE) was investigated in comparison with other tumor markers (CEA, CT, CA 15-3) used in the diagnosis and treatment monitoring of lung cancer. As previously described, the calcitonin assay proved to have very low sensitivity for small cell lung cancer (SCLC). The serum NSE assay was, however, shown to be a useful diagnostic aid for discrimination between histologically different lung cancers, and therefore this assay may be a valuable tool for treatment monitoring in SCLC patients. CA 15-3, also an unspecific marker, showed similar sensitivity to the NSE assay in SCLC patients, the sensitivity being higher than CEA in non small cell lung cancer (NSCLC).     

Use of tumor markers in the management of head and neck cancer

Serologic tumor markers have been evaluated in the diagnosis, management and follow-up of patients with head and neck cancer. However, to the authors' knowledge no tumor marker has yet been shown to be useful for monitoring the response to chemotherapy in this type of disease, in particular for undifferentiated tumors. The pretreatment levels of CEA, TPA, SCC and ferritin were evaluated in 98 patients with advanced head and neck cancer. Of this group 64 patients were studied sequentially every month during planned chemotherapy and three weeks after treatment using standard commercial kits. The results showed the following sensitivity values: TPA 50%, CEA 36%, SCC 34% and ferritin 19%. The incidence and magnitude of the marker elevations were correlated with the extent of disease. In patients with squamous cell cancer SCC and CEA were elevated (by 68% and 54%, respectively) in tumors with good differentiation (G1), but only by 13% (both markers) in tumors classified as poorly differentiated (G3). CEA, SCC and ferritin serum levels were not correlated with response to chemotherapy, while TPA values correlated with the clinical response to treatment in 100% of patients with undifferentiated cancer and in 75% of those with squamous cell cancer. Our data indicate that in patients with head and neck cancer TPA appears to be a sensitive marker, followed in decreasing order of sensitivity by CEA, SCC and ferritin. However, SCC and CEA seem to be the most suitable markers for squamous cell cancer and in particular for more differentiated tumors (G1). Finally, TPA has proved to be a useful marker for monitoring the response to chemotherapy in patients with head and neck cancer, in particular for undifferentiated tumors.     

Tumor markers and lung cancer: correlation between serum and bronchial secretion levels of CEA, TPA, CanAg CA-50, NSE and ferritin

The levels of carcinoembryonic antigeny (CEA), tissue polypeptide antigeny (TPA), CanAg 50, neuron specific enolase (NSE) and ferritin were determined in bronchial secretion and serum of patients with neoplastic and non-neoplastic lung diseases. Simultaneous determination of two or three markers in the serum and in bronchoalveolar lavage (BAL) may be clinically useful for the diagnosis of lung cancer and even for the type of tumor. The positivity of CEA determined simultaneously in serum and in BAL of patients with lung cancer is higher than 80% whereas in patients with benign lung disease it is lower than 40%. The simultaneous assay of TPA in serum and in BAL showed 100% positivity in patients with oat-cell carcinoma, the frequencies of positivity were similar in patients with non-oat-cell carcinoma. For NSE and CanAg CA-50 patients with oat-cell carcinoma showed 100% positivity. Simultaneous assay of ferritin in serum and in BAL gave 85% positivity in patients with oat-cell carcinoma and only 23% in patients with non-oat-cell carcinoma. We conclude that the simultaneous determination of CEA and CanAg CA-50 or NSE in serum and in BAL is a useful aid in the diagnosis of lung malignancy.     

Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.     

Comparative analysis of certain metals and tumor markers in bronchopulmonary cancer and colorectal cancers. Metals and tumor markers in the neoplastic process

Carcinogenic metal levels in serum and tissue samples were measured in patients with bronchopulmonary or colorectal cancer. The cadmium and nickel tissue levels in the patients with lung cancer were significantly higher than in the controls. A statistical correlation was found between chromium and cadmium, as well as between cadmium and nickel in patients with colorectal cancer. In addition, prior to the operation, the tumor markers alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (Ca 19-9), polypeptide histidio antigen (TPA) and ferritin were analyzed. Their average concentrations were correlated with the existing concentrations of the metals. This was done for both types of cancer. Tumor marker detection showed an increase of CEA and TPA in patients with colorectal cancer. A statistical correlation was observed between AFP and zinc tumor tissue.     

A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary Diagnosis of Small Cell Lung Cancer

Background

Lung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity.

Methods

We used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na⁺, Cl^-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC.

Results

After appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients.

Conclusion

We have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use for detection of SCLC in less developed regions.     

Early diagnosis of lung cancer by detection of tumor liberated protein

Tumor liberated protein (TLP) is a protein that can be used to reveal the early development of a tumor. Besides being formed in the tumor, TLP is released in the blood when a patient starts producing cancer cells, which in turn enables the physician to intervene at a stage when the cancer is operable. To date, the available studies of tumor markers in lung cancer patients are CEA, NSE, TPA, Chromogranine, CA125, CA19-9, and Cyfra 21-1. The sensitivity and specificity for serum markers ranges between 50 and 90%, depending on the study and the clinical samples analyzed. Most of these markers show an increased rate of positivity as the stage advances. There are very limited data on TLP to draw any firm conclusion regarding the diagnostic value of this marker. TLP has been detected in 53.1% of non-small cell lung cancer (NSCLC) patients (N = 534) with 75% being positive in the early stage (stage I) and dropping to 45% in the late stage (stage IV). However, 7.6% blood donor sera and 17.4% chronic lung disease sera have also tested positive. In a confirmation study, the specificity was 89.94% and the sensibility was 63.63% from stage III to IV NSCLC patients. In an initial study of TLP as a marker for early detection in stage I, NSCLC patients showed a sensitivity of 66.7% and a specificity of 80% for TLP compared to a sensitivity of 33.3% for CA19-9, 11.1% for Cyfra 21-1 and CA125, and 0% for CEA; the specificity for all four of the latter markers was 100%. Using immunohistochemical analysis with peroxidase anti-peroxidase (PAP), we observed that NSCLC cells were positive; we used the specific rabbit antiserum to TLP, which turned out negative in the presence of 1 mg/ml of the synthetized peptide. The pre-serum was also negative. The same reactivity was found early in the modified epithelial cells of interstitial lung fibrosis and might be a predictive marker of cell transformation. The site of the peroxidase positivity was cytoplasmic, of diffuse and/or granular type.     

多种血清肿瘤标志物联合检测对肺癌诊断的临床意义分析

目的:探讨CA125、CYFRA21-1、CEA、NSE、AFP联合检测对肺癌的诊、诊断的敏感度以及特异性。方法:对我院收治的确诊为肺癌的患者选取120例作为A组,同期选择肺部良性病变患者61例作为B组,以及50例健康体检患者作为C组,将三组研究对象分别进行CA125、CYFRA21-1、CEA、NSE、AFP的检测。结果:A组患者CA125、CYFRA21-1、CEA、NSE、AFP的血清中含量明显高于B组以及C组(P<0.05);五种标记物联合检测的敏感度明显高于单一标志物的敏感度(P<0.05),但其特异性有明显的降低(P<0.05)。结论:采用CA125、CYFRA21-1、CEA、NSE、AFP联合检测,对肺癌的早期诊断以及治疗预后有较好的指导作用。     

Ⅲ期非小细胞肺癌患者精确放疗前后血清CEA、SCC、NSE水平变化及与放疗疗效的关系研究

目的:研究Ⅲ期非小细胞肺癌(NSCLC)患者精确放疗前后血清癌胚抗原(CEA)、鳞状细胞癌相关抗原(SCC)、神经元特异性烯醇化酶(NSE)水平变化及与放疗疗效的关系。方法:选择2014年1月到2016年12月在亳州市人民医院肿瘤科就诊的60例Ⅲ期NSCLC患者纳入此次研究,其中鳞癌14例,腺癌26例,腺鳞癌20例。所有患者均实施4周的精确放疗,放疗后肿瘤标记物水平降低43例,升高17例。根据放疗疗效将患者分为有效组39例,无效组21例。对比不同病理类型的Ⅲ期NSCLC患者CEA、SCC、NSE水平,不同疗效组放疗前后CEA、SCC、NSE水平,并分析患者的肿瘤标记物水平变化与放疗疗效的关系。结果:腺癌Ⅲ期NSCLC患者的CEA、NSE水平高于鳞癌及腺鳞癌者,且腺鳞癌者又高于鳞癌者;SCC水平低于鳞癌及腺鳞癌者,且腺鳞癌者又低于鳞癌者(P0.05)。放疗后有效组CEA、SCC、NSE水平均低于放疗前和无效组,而无效组CEA、SCC、NSE水平高于放疗前(P0.05)。肿瘤标记物水平降低者的有效率高于升高者,差异有统计学意义(P0.05)。结论:在实施精确放疗后治疗有效的Ⅲ期NSCLC患者,其血清CEA、SCC、NSE水平均呈现出明显的下降趋势,且与病理类型密切相关,临床上可重点关注上述指标水平,有助于患者的诊疗过程。     

CYFRA21-1 can predict the sensitivity to chemoradiotherapy of non-small-cell lung carcinoma

Background: The increasing panel of systemic therapies enables the individual management of lung cancer patients, even in advanced stages. However, predictive tools indicating the efficacy of chemoradiotherapy (CRT) are badly needed.

Aims: To determine the tumour markers for predicting the therapeutic effect in non-small-cell lung carcinoma (NSCLC) patients treated with CRT.

Methods: The serum levels of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), neurone-specific enolase (NSE) and carcinoembryonic antigen (CEA) were measured before CRT by enzyme-linked immunosorbent assays, while the tumour responses were assessed according to the World Health Organization (WHO) response criteria. The relationships between pretreatment expression of CYFRA21-1, NSE, CEA and the effectiveness of CRT were analysed.

Results: The complete response (CR) rate of the primary tumours estimated by computed tomography in patients with high levels of CYFRA21-1 was 2.9% (2/68) while in cases with low CYFRA21-1 it was 20.3% (12/59) (p?=?0.005). The effective rates (CR+PR) in CYFRA21-1 high and low groups were 52.9% (36/68) and 72.9% (43/59), respectively (p?=?0.022).

Conclusions: CYFRA21-1 may be a reliable surrogate marker of CRT efficacy in patients with NSCLC.     

Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were collected from 169 NSCLC patients. CTCs were detected by CellSearch and tumor markers were detected using the Luminex xMAP assay. Univariate analyses revealed that histology, tumor stage, tumor size, invasiveness, tumor grade and carcinoembryonic antigen (CEA) were associated with the presence of CTCs. However, the level of CTCs was not associated with the degree of nodal involvement (N) or tumor prognostic markers Ki-67, CA125, CA199, Cyfra21-1, and SCCA. Using logistic regression analysis, we found that the combination of CTCs with tumor marker CEA has a better disease prediction. Advanced stage NSCLC patients with elevated CEA had higher numbers of CTCs. These data suggest a useful prediction model by combining CTCs with serum CEA in NSCLC patients.     

Immunoradiometric assay of chromogranin A in the diagnosis of small cell lung cancer: comparative evaluation with neuron-specific enolase

The aims of our work were 1) to determine the diagnostic performance of an immunoradiometric assay of chromogranin A (CgA) in small cell lung cancer and 2) to compare its discriminatory power with that of neuron-specific enolase (NSE), the marker currently used for SCLC. We selected 166 cases of small cell (64) and non-small cell (102) lung cancer and 106 cases of non-malignant lung diseases as controls. Both CgA and NSE were assayed by immunoradiometric methods and cutoff values were established on the basis of a pre-fixed specificity of 95% in non-malignant lung diseases. The CgA assay showed better diagnostic sensitivity than NSE in SCLC (61% versus 57%), especially in limited disease, and a low positivity rate in NSCLC with respect to NSE (14% versus 22%). By contrast, NSE reflected disease extent more accurately than CgA (U test: CgA p<0.05, NSE p<0.001). Finally, we found that the CgA assay was not affected by hemolysis whereas NSE serum levels greatly increased in hemolyzed sera. In conclusion, CgA assaying by an IRMA method is a reliable procedure in the diagnosis of SCLC. NSE remains the marker of choice in staging and monitoring of the disease. Further studies are needed to evaluate the prognostic significance of the marker and its role in therapy monitoring and patient follow-up.     

神经元特异性烯醇酶和癌胚抗原胶体金免疫层析联合检测

目的:应用双抗夹心胶体金免疫层析方法,实现对神经元特异性烯醇化酶(NSE)和癌胚抗原(CEA)两种肺癌肿瘤标志物的快速联合检测。方法:采用柠檬酸三钠还原法制备20nm胶体金颗粒,并分别对鼠抗NSE、CEA单克隆抗体进行标记,分别与之相配对的另一种单克隆抗体被喷在硝酸纤维素膜(NC膜)上,制成免疫层析检测试条。溶液中的抗原NSE、CEA与金标记抗体结合后沿着硝酸纤维素膜移动,与膜上固定的抗体结合形成肉眼可见的红色线条。结果:该试纸条只与NSE、CEA有特异性反应,与CA125、CYFRA21-1、TPA等肺癌标志物无交叉反应。标准样品中两种抗原的检测灵敏度分别可达到5ng/mL和3ng/mL。结论:胶体金免疫层析技术检测NSE、CEA特异性强、灵敏度高、简便快速,不需特殊仪器设备,有广泛应用价值。     

神经元特异性烯醇酶和癌胚抗原胶体金免疫层析联合检测

目的：应用双抗夹心胶体金免疫层析方法,实现对神经元特异性烯醇化酶（NSE）和癌胚抗原（CEA）两种肺癌肿瘤标志物的快速联合检测。方法：采用柠檬酸三钠还原法制备20nm胶体金颗粒,并分别对鼠抗NSE、CEA单克隆抗体进行标记,分别与之相配对的另一种单克隆抗体被喷在硝酸纤维素膜（NC膜）上,制成免疫层析检测试条。溶液中的抗原NSE、CEA与金标记抗体结合后沿着硝酸纤维素膜移动,与膜上固定的抗体结合形成肉眼可见的红色线条。结果：该试纸条只与NSE、CEA有特异性反应,与CA125、CYFRA21-1、TPA等肺癌标志物无交叉反应。标准样品中两种抗原的检测灵敏度分别可达到5ng/mL和3ng/mL。结论：胶体金免疫层析技术检测NSE、CEA特异性强、灵敏度高、简便快速,不需特殊仪器设备,有广泛应用价值。     

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.     

血清NSE、SCCA及CEA在肺癌早期诊断和预后预测中的应用价值研究

目的:研究血清神经元特异性烯醇化酶(NSE)、鳞状细胞癌抗原(SCCA)及癌胚抗原(CEA)在肺癌早期诊断和预后预测中的应用价值。方法:选择我院2013年1月~2017年1月收治的110例肺癌患者(肺癌组)及同期96例肺部良性疾病患者(肺良性病组)和85例门诊健康体检者(对照组)。比较各组血清NSE、SCCA及CEA水平,采用受试者工作特征(ROC)曲线分析以上指标对肺癌的诊断价值。结果:肺癌组血清NSE、SCCA、CEA水平高于肺良性病组及对照组,肺良性病组血清NSE、SCCA、CEA水平高于对照组(P<0.05)。肺癌Ⅲ+Ⅳ组血清NSE、SCCA及CEA水平高于Ⅰ+Ⅱ组(P<0.05)。小细胞肺癌组血清NSE水平高于鳞癌组、腺癌组,鳞癌组血清SCCA水平高于腺癌组及小细胞肺癌组,腺癌组血清CEA水平高于鳞癌组及小细胞肺癌组(P<0.05)。NSE<16.0μg/L者平均无疾病进展生存期(PFS)长于NSE≥16.0μg/L,SCCA<1.5μg/L者平均PFS长于SCCA≥1.5μg/L,CEA<5.0μg/L平均PFS长于CEA≥5.0μg/L(P<0.05)。NSE、SCCA和CEA及三者联合诊断肺癌的ROC曲线下面积分别为0.880、0.651、0.830及0.937,NSE+SCCA+CEA联合诊断的曲线下面积高于单个指标单独诊断(P<0.05)。结论:血清NSE、SCCA及CEA对肺癌的诊断有重要的参考价值,且有利于肺癌的分期、分型及预后评价。     

CEA is an Independent Prognostic Indicator that is Associated with Reduced Survival and Liver Metastases in SCLC

Small-cell lung cancer (SCLC) is classified into two stages, limited-stage small-cell lung cancer (LS-SCLC) and extensive-stage small-cell lung cancer (ES-SCLC), with ES-SCLC being associated with reduced survival. However, disease stage alone is not a very precise predictor of survival time. The aim of this study is to search for a prognostic indicator that can be used in conjunction with the staging system in SCLC. We performed a prospective analysis of 116 patients with SCLC undergoing standard chemotherapy with or without radiotherapy. Expression levels of 12 tumor markers were measured at the time of diagnosis by a commercial protein chip system, and patients were followed up for a maximum of 54 weeks. CEA was the most frequently detected tumor marker in SCLC, with 32.8% of samples scoring positive, and was also the only marker that correlated with overall survival. The average survival time was 16.78 months for patients with CEA below 5 ng/ml and 11.4 months for patients with CEA above 5 ng/ml (P < 0.001). In contrast, no association was found between tumor stage and overall survival. CEA expression was independent of tumor stage (P = 0.930). CEA is an independent prognostic factor that can be used in conjunction with disease stage in SCLC.     

Carcinoembryonic antigen, ferritin, tissue polypeptide antigen, and CA15/3 in breast cancer: relationship between carcinoma and normal breast tissue

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmunometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when non-malignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.     

血清肿瘤标志物在肺癌辅助诊断中的应用

目的探讨血清肿瘤标志物在肺癌诊断中的临床价值。方法收集40例健康人、45例肺部良性疾病患者和90例肺癌患者,采用电化学发光分析检测患者血清中肿瘤标志物细胞角蛋白19(CYFRA21-1)、鳞状细胞癌相关抗原(SCC)和癌胚抗原(CEA),以及胃泌素释放肽前体(pro-GRP)和神经元特异性烯醇化酶(NSE)的含量。结果健康人组和肺部良性疾病患者组血清NSE、pro-GRP、CYFRA21-1、SCC和CEA水平较肺癌患者组水平低,差异有统计学意义(P0.01)。NSE和pro-GRP在小细胞肺癌患者中的水平均明显高于其他类型的肺癌患者(P0.01),CYFRA21-1和SCC在鳞癌患者中的含量比其他类型肺癌患者高(P0.01)。联合检测此5种血清肿瘤标志物敏感性高于单独的肿瘤标志物(P0.01)。结论联合检测NSE、pro-GRP、CYFRA21-1、SCC和CEA可以提高肺癌诊断的灵敏度。