Prognostic Significance of a Tumor Marker Index Based on Preoperative Serum Carcinoembryonic Antigen and Krebs von den Lungen-6 Levels in Non-Small Cell Lung Cancer

Background: We retrospectively analysed the prognostic significance of a tumor marker index (TMI) based on preoperative serum carcinoembryonic antigen (CEA) and Krebs von den Lungen-6 (KL-6) levels in nonsmall cell lung cancer (NSCLC) patients. Materials and Methods: We enrolled 176 NSCLC patients who had preoperative serum CEA and KL-6 level measurements and had undergone curative surgery between 2009 and 2011. Results: The 5-year disease-specific survival of patients with high serum CEA levels was significantly poorer compared with that of patients with normal levels. The value for patients with high serum KL-6 levels was also poor. Patients with both normal serum CEA and KL-6 levels had a favourable prognosis, whereas those with both high serum CEA and KL-6 levels had a poor outcome. The5-year disease-specific survival rate was 82.9% for patients in the low TMI group compared to 47.5% in the high TMI group (p<0.01). Both univariate and multivariate analyses revealed prognostic significance for TMI. Conclusions: TMI based on preoperative serum CEA and KL-6 levels might be useful for the prediction of the prognosis of NSCLC patients.     

Detection of a circulating tumor-associated antigen with a murine monoclonal antibody, LISA 101, selected by reversed indirect enzyme-linked immunosorbent assay

In the presence of a characterized monoclonal antibody recognizing a soluble molecule, additional monoclonal antibodies reactive with unknown antigenic determinants on the molecule can be easily selected by reversed indirect enzyme-linked immunosorbent assay. A novel murine monoclonal antibody, LISA 101, was selected by reversed indirect enzyme-linked immunosorbent assay against soluble antigens, which exist in sera and in pleural effusions derived from lung adenocarcinoma patients and which bear determinants recognized by the previously characterized murine monoclonal antibody KL-6. Antigenic determinants recognized by the LISA 101 antibody appear to be sialylated carbohydrate in nature and different from those recognized by previously reported monoclonal antibodies against sialylated carbohydrates, such as NS 19-9, FH-6, and KL-6, suggested by competitive inhibition assay and immunostaining of tissues. A circulating antigen, LISA 1-6, was detected by a bimonoclonal bideterminant assay using immobilized LISA 101 antibody and enzyme-labeled KL-6 antibody. It was found that serum LISA 1-6 levels were elevated in 63% (25 of 40) of patients with lung adenocarcinoma and in 92% (11 of 12) of patients with pancreatic carcinoma, but only in 6.5% (2 of 31) of patients with benign lung diseases and in 7.1% (1 of 14) of patients with pancreatitis. The present observations indicate that the LISA 1-6 antigen may serve as a new tumor marker for adenocarcinomas of the lung and the pancreas. Additionally, the reversed indirect enzyme-linked immunosorbent assay may be a widely applicable method for selecting new monoclonal antibodies against as yet unknown antigenic determinants on soluble molecules.     

Evaluation of serum KL-6, a mucin-like glycoprotein, as a tumor marker for breast cancer.

The utility of serum KL-6 as a tumor marker for breast cancer was evaluated in this study. The sera from 146 patients with breast cancer, 13 with benign breast disease, and 108 healthy individuals were measured for KL-6 titer using a sandwich enzyme immunoassay method. Carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) titers were also tested in the same sera from the patients. The mean KL-6 titer of patients with primary breast cancer was 673 units/ml, which was significantly higher than that of benign and healthy individuals (P = 0.037 and P < 0.0001, respectively). The titer of patients with relapsed breast cancer was 1964 units/ml, which was also higher than that of primary cancer (P = 0.013). KL-6 titer was related to tumor stage, distant metastasis, and relapse site (P = 0.0053, P < 0.0001, and P = 0.0251, respectively). Using the cutoff value of 467 units/ml, the sensitivity of KL-6 was 31% for primary breast cancer (16% for stage I and 29% for stage II) and 73% for relapsed breast cancer (50% for local relapse and 89% for distant relapse). The specificity was 92%. The sensitivity of KL-6 was higher than that of CA15-3 and CEA. Combination of the three markers, followed by KL-6 and CEA, raised the sensitivity for primary breast cancer. Single use of KL-6 demonstrated a higher sensitivity than in each combination for relapsed breast cancer. In conclusion, serum KL-6 may be helpful for clinical use as a tumor marker for breast cancer, and it may play an important role, especially in the surveillance of disease relapse.     

Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer

By immunizing mice with a lung adenocarcinoma cell line, we previously established a murine IgG1 monoclonal antibody that recognizes a sialylated sugar chain designated Krebs von den Lungen-6 (KL-6). KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. The aim of this study was to determine whether KL-6 expression in tumors correlates with circulating KL-6 levels and whether circulating KL-6 has any prognostic value in patients with surgically resected non-small cell lung cancer (NSCLC). Immunohistochemical analysis of KL-6 expression was performed on 103 NSCLC tissues, and its associations with serum KL-6 levels and survival were examined. We also evaluated whether KL-6 expression patterns and/or serum KL-6 levels could predict prognosis in these NSCLC patients. Immunohistochemical analysis of KL-6 in NSCLC tissues showed that a depolarized KL-6 expression pattern was associated with a high level of circulating KL-6 and a poor prognosis in NSCLC patients who underwent curative surgery. Furthermore, a high circulating KL-6 level was associated with both poorer progression-free survival (PFS) and overall survival (OS), and multivariate analyses confirmed its independent prognostic value for both PFS and OS (p = 0.041 and 0.023, respectively). Our data suggest that preoperative serum KL-6 level reflects KL-6 expression patterns in NSCLC tissue, and can serve as a useful prognostic biomarker in NSCLC patients who undergo curative surgery.     

A circulating heat-resistant mucin-like antigen in patients with lung-cancer detected by a new murine monoclonal-antibody

We discovered a circulating mucin-like antigen designated as CAM-14 detected by a new murine monoclonal antibody KL-14 (IgM). We found different heat resistant properties between serum CAM- 14 from normal individuals and from lung cancer patients. Heat treatment had less effect on the levels of CAM-14 in sera from lung cancer patients, whereas CAM-14 levels in sera from normal individuals were markedly decreased after heat treatment at tempratures > 65-degrees-C. As a serum tumor marker, CAM- 14 had only very low levels of false-positive values with a high specificity and effectively increased the positive rate for lung cancer patients when used together with carcinoembryonic antigen.     

Tumor markers in lung cancer]

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA), and pro-gastrin-releasing peptide (proGRP) can be used as tumor markers for lung cancer. CEA is sensitive for adenocarcinoma, SCC and CYFRA for squamous cell carcinoma, and NSE and proGRP for small cell carcinoma. A tumor marker is generally used as a marker to monitor the clinical course. Serum levels of pro-GRP, reflect the disease course of patients with small cell lung cancer more accurately than NSE or CEA. Among the patients with clinical N0-1 non-small cell lung cancer high serum CEA levels, adenocarcinoma histology, and large tumor dimension were significant predictors of pathologic N2 disease. CEA played a new role in predicting metastasis to mediastinal lymph nodes A more effective treatment may enhance the value of tumor markers to predict relapse.     

Clinical significance of the number of positive tumor markers in assisting the diagnosis of lung cancer with multiple tumor marker assay

The clinical significance of multiple tumor marker assay in assisting the diagnosis of lung cancer was assessed in 67 patients with primary lung cancer, and 115 with nonmalignant pulmonary disease. The tumor markers studied were carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma-related antigen (SCC), and tissue polypeptide antigen (TPA). The positive rates for all of the tumor markers were significantly higher in the lung cancer group than in the nonmalignant pulmonary disease group. The sensitivity was 31-66%, the specificity was more than 90% for all five markers, and the accuracy was 69-82%. Among the markers, the positive rate of CEA was best correlated with adenocarcinoma (Ad), NSE with small cell carcinoma (Sm), SCC with squamous cell carcinoma (Sq), CA19-9 with Ad, and TPA with Ad. In multiple tumor marker assay, as the number of combined markers was increased, the sensitivity of the assay became higher and the specificity became lower, resulting in a lower accuracy. However, when more than two markers were positive, the relative possibility of lung cancer was increased 90-100%. The number of positive tumor markers in multiple tumor marker assay indicated that it would be of auxiliary value for the diagnosis of lung cancer.     

KL-6在肿瘤中的研究进展

KL-6是由MUCl基因编码,相对分子量接近200000的糖蛋白。很早就已作为间质性肺疾病的血清学指标。近年来研究发现,KL-6在乳腺癌、肺癌、结肠癌、壶腹部癌等多种肿瘤中表达均增高,而且同有无淋巴结转移、远处转移密切相关。检测血清KL-6有助于了解乳腺癌、结肠癌等肿瘤的疾病发展和检测,并可以对肺癌某些靶向药物的疗效评估有预测作用。对于放射性肺炎有一定的预测作用。     

Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors

Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein classified in the category of human MUC1 mucin. KL-6 has been reported to serve as a sensitive marker for interstitial pneumonia; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. To further elucidate the clinicopathological significance of circulating KL-6 in lung cancer, we monitored the circulating KL-6 levels in advanced nonsmall cell lung cancer (NSCLC) patients and analyzed the association between these levels and the clinical outcome of EGFR-TKI treatment. The pretreatment levels of circulating KL-6 were found to be significantly higher in progressive disease (PD) patients than disease-controlled (partial response (PR) and stable disease (SD)) patients. Multivariate analyses revealed the circulating KL-6 level to be an independent prognostic factor for overall survival as well as progression-free survival. In addition to these observations, we found that changes in circulating KL-6 levels at 2 weeks after the start of EGFR-TKI treatment from the baseline could quite precisely discriminate PD cases from PR or SD patients and the clinical outcome of EGFR-TKI in NSCLC patients. These results indicate that the monitoring of circulating KL-6 levels in NSCLC patients is effective for both selecting patients to be treated with EGFR-TKI and predicting the clinical outcome of EGFR-TKI. In addition, the findings suggest that the circulating KL-6 level could be used as a clinically relevant biomarker in patients with NSCLC, particularly those who are candidates for EGFR-TKI treatment.     

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。     

Detection of Soluble Tumor-associated Antigens in Sera and Effusions Using Novel Monoclonal Antibodies, KL-3 and KL-6, against Lung Adenocarcinoma

Two novel monoclonal antibodies, KL-3 (IgM) and KL-6 (IgG¹),which can detect soluble antigens in sera and effusions (molecularweights > 1,000 K) were produced against human pulmonaryadenocarcinoma VMRC-LCR cells. KL-3 and KL-6 antibodies reactedwith asialo- and sialo-carbohydrate antigenic determinants,respectively. Both carbohydrate epitopes appear, from competitiveinhibition studies, to be different from Le^x, Le^y, sialyl Le^aand sialyl Le^xi which were recognized with FH2, AH6, NS19-9and FH6 antibodies, respectively. Using an enzyme linked immunosorbentassay, elevated KL-6 antigen levels were frequently observedin the sera of patients with lung adenocarcinoma [52% (17/33)],pancreatic cancer [44% (4/9)] and breast cancer [40% (8/20)],but infrequently in the sera of patients with lung squamouscell carcinoma [18% (4/22)], lung small cell carcinoma [8% (1/13)],gastric cancer [0% (0/19)], colorectal cancer [0% (0/8)] andhepatocellular cancer [13% (1/8)]. The levels and positive ratesof scrum KL-6 antigen increased with the progression of clinicalstage of lung adenocarcinoma. In pleural effusions, the prevalencesof lung adenocarcinoma cases with elevated levels of KL-3 andKL-6 antigens were 76% (13/17) and 82% (14/17), respectively.These monoclonal antibodies can define novel soluble antigensin sera and effusions which could be useful in tumor diagnosesand for monitoring tumor progression.     

胸水和血清CEA、CA125、CYFRA21-1、NSE和Pro-GRP联合检测对肺癌的诊断价值

目的:探讨联合检测肺癌胸水和血清中癌胚抗原(CEA)、癌抗原125(CA125)、细胞角蛋白19片段(CYFRA21-1)、神经原特异性烯醇化酶(NSE)和胃泌素释放肽前体(Pro-GRP)5 种肿瘤标志物水平在肺癌临床诊断中的应用价值,以期提高鉴别良恶性胸水的能力。方法:用电化学发光法检测93例肺癌患者和54例肺炎性疾病患者的血清及胸水标本CEA、CA125、CYFRA21-1、NSE和Pro-GRP水平。结果:癌性胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物平均水平与炎性胸水组比较,差别均有统计学意义(P<0.05);癌性胸水组中CEA、CYFRA21-1、CA125的含量远远高于炎性胸水组（20~600倍）(P<0.01)。肺癌胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物水平与肺癌血清组比较,差别均有统计学意义(P<0.05)。肺癌胸水组中CEA、CYFRA21-1、CA125的含量远远高于肺癌血清组（7~80倍）(P<0.01),相比与正常对照组更是有200倍以上的增高(P<0.01),因此胸水中CEA、CYFRA21-1、CA125百倍左右的升高提示恶性肿瘤的存在。将93例癌性胸水和血清分为腺癌、鳞癌和小细胞癌。腺癌、鳞癌和小细胞癌胸水组中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物含量明显高于炎性胸水组(P<0.01);腺癌胸水组中CEA含量明显高于鳞癌和小细胞癌(P<0.01);鳞癌胸水组中CYFRA21-1含量明显高于腺癌和小细胞癌(P<0.01);小细胞癌胸水组中NSE和Pro-GRP含量明显高于腺癌和鳞癌(P<0.01)。CA125含量在胸水组中腺癌、鳞癌含量明显高于小细胞癌(P<0.01)。5 种标志物单项及联合检测的灵敏度肺癌胸水组均高于肺癌血清组,肺癌胸水中5项联合检测后灵敏度可达99.11%。结论:肺癌组胸水中CEA、CA125、CYFRA21-1、NSE和Pro-GRP 5种肿瘤标志物联合检测有利于良恶性胸水的鉴别诊断,联合检测可以提高肺癌诊断的灵敏度,当肿瘤标志物显著升高时,CEA可作为肺腺癌的肿瘤标志物;CYFRA21-1可作为肺鳞癌的肿瘤标志物;NSE和Pro-GRP可作为小细胞癌的肿瘤标志物;CA125可作为非小细胞肺癌的肿瘤标志物。     

胸水CA125、CA199、CEA、NSE、CYFRA21-1、CA72-4对原发性肺癌的诊断价值

目的探讨胸水中糖链抗原125（CA125）、糖链抗原199（CA199）、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）和糖链抗原72-4（CA72-4）在原发性肺癌并胸腔积液的诊断和鉴别诊断、病理分型中的价值。方法采用电化学免疫荧光发光法同时检测90例原发性肺癌并胸腔积液患者（恶性胸腔积液组）和64例良性胸腔积液患者（良性胸腔积液组）胸水中CA125、CA199、CEA、NSE、CYFRA21-1和CA72-4水平。结果恶性胸腔积液组各胸水肿瘤标志物水平均高于良性胸腔积液组（P〈0．05）,其中CEA、CYFRA21-1、NSE分别对腺癌、鳞癌、小细胞肺癌最敏感。联合检测以CEA＋NSE＋CYFRA21-1最优,可使敏感性达98．9％,阴性预测值至96．6％,准确性提高至76．0％。结论胸水肿瘤标志物在原发性肺癌的诊断中价值较高,其中CEA的诊断价值最大,联合检测诊断准确性优于单项检测。     

A novel monoclonal antibody, H9, directed against the core protein of MUC1 mucin

MUC1 mucin is a target protein for many monoclonal antibodies. Human MUC1 detected by a murine anti-KL-6 monoclonal antibody that recognizes a sialylated carbohydrate chain has been designated KL-6/MUC1. Given the heterogeneous antigenicity of KL-6/MUC1, we established a new murine monoclonal antibody, H9, that reacts with epitope DTRP (Asp-Thr-Arg-Pro) peptides within the immunodominant region of the tandem repeat of MUC1 mucin. The reactivity of the H9 antibody differs from that of other previously reported antibodies that recognize the tandem repeat region of MUC1. Immunohistochemical experiments indicate that the reactivity of the H9 antibody is similar to that of other antibodies directed against MUC1 core proteins. A new cancer-associated protein detected by a sandwich assay using the H9 antibody as a catcher and the KL-6 antibody as a tracer is designated HK9. Serum HK9 levels showed a high expression level in lung cancer: 51% (19/37 cases) for adenocarcinoma, 39% (11/28 cases) for squamous cell carcinoma, and 67% (10/15 cases) for small cell carcinoma. The HK9 expression in lung cancer increased with cancer progression. These findings suggest monoclonal antibody H9 to be a novel antibody that reacts with an epitope within the tandem repeat region of MUC1, and that the cancer-associated antigen HK9 may have useful tumor-associated properties.     

Clinical Utility of Haptoglobin in Combination with CEA,NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers,haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19fragment (CYFRA21-1). Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE,CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patientswith benign lung disease and 150 healthy controls. Differences of expression were compared among groups,and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Results: Serum tumormarker levels in patients with lung cancer were obviously higher than those with benign lung disease and normalcontrols (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%,with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce apositive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, thepositive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinomacase , the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, thepositive detection rate of NSE was highest. The area under receiver operating characteristic curve (AUCROC) ofHp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665).Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA,NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, andcould be useful for pathological typing.     

Utility of the serum tumor markers: CYFRA 21.1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in squamous cell lung cancer

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.     

Detection of tumor associated antigen, PA8-15, in sera from pancreatic and gastrointestinal carcinoma patients

A sandwich enzyme immunoassay was set up to measure tumor associated antigen (antigen PA8-15) detected by monoclonal antibody PA8-15. The cut-off value was set at 55 U/ml. Tests on 437 sera samples from patients with malignant or benign diseases yielded the following positive percentages: esophageal cancer, 9.1%; gastric cancer, 23.1%; colorectal cancer, 44.8%; hepatoma, 32.6%; biliary tract cancer, 47.5%; pancreatic cancer, 84%; lung cancer, 30.8%; breast cancer, 16%; benign diseases, 13.2%. Positive antigen PA8-15 levels in patients with gastric, colorectal and pancreatic cancers, increased with the progression of clinical stage. When antigen PA8-15 was monitored in 11 various cancer cases before and after surgery, a decrease in PA8-15 value was revealed in all resected patients postoperatively, whereas a more than 100% increase in PA8-15 values was noted in non-resected patients. Compared with CEA and CA19-9, the highest positive PA8-15 rate was seen in pancreatic cancer patients. By combining the rates of positive sera obtained with each tumor marker, the overall percentage increased. These results suggest that measuring serum PA8-15 levels will aid in serological cancer diagnoses, particularly pancreatic cancer.     

非小细胞肺癌血清中CA125、CEA的浓度及意义

背景与目的CA125、CEA是最早被应用的肿瘤标志物,目前认为CEA在腺癌中有较高的表达,对近3年住院的非小细胞肺癌患者病历进行回顾性分析,发现CA125在非小细胞肺癌中的阳性率远高于以往文献报道。本文旨在讨论非小细胞肺癌血清中CA125、CEA的浓度及意义。方法应用化学发光法检测136例非小细胞肺癌患者,46例肺部良性病变患者及50例健康体检者血清中CA125、CEA含量。结果非小细胞肺癌患者血清CA125含量明显高于肺部良性病变(混合细胞癌除外),差异有统计学意义(P<0.0001),CEA在腺癌及鳞癌患者血清中的含量明显高于肺部良性病变,差异有统计学意义(P<0.0001),CA125、CEA含量在肺部良性病变患者与健康体检者之间无明显差异。CA125在大细胞癌、腺癌、鳞癌、混合细胞癌中的阳性率分别为92.3%、80.2%、54.8%、50%,CEA在腺癌、大细胞癌、鳞癌、混合细胞癌中的阳性率分别为67.4%、0、25.8%、0,CA125/CEA联合检测能提高腺癌的阳性率(90.7%)。进展期非小细胞肺癌CA125、CEA阳性率分别为86.9%、63.6%,CA125在进展期腺癌阳性率达90.9%。结论CA125在非小细胞肺癌中的阳性率较CEA高,在进展期大细胞癌和腺癌中敏感性在90%以上,在协助非小细胞肺癌的诊断中,检测CA125比CEA更有意义。     

Diagnostic values of SCC, CEA, Cyfra21-1 and NSE for lung cancer in patients with suspicious pulmonary masses: a single center analysis

We recruited 805 patients with suspicious pulmonary masses that were identified finally as lung cancer or benign pulmonary masses. The serum levels of four tumor markers, including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1) and neuron specific enolase (NSE) were tested for every patient. Though receiver operating characteristic (ROC) curves indicated unsatisfactory diagnostic power of those four tumor markers for lung cancer, 37.3% of early-staged lung cancer could be diagnosed just on the combination assays of the four tumor markers, under adjusted cut-off values through our statistical analysis retrospectively.     

联合检测肿瘤标志物在胸腔积液中的应用价值

目的:探讨胸腔积液中肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片断(CYFRA21-1)、神经元特异性烯醇化酶(NSE)检测在胸腔积液诊断中的价值。方法:应用电化学发光法对65例肺癌患者和28例良性对照者的血清和胸腔积液进行检测。结果:肺癌组中血清和胸水肿瘤标志物明显高于对照组(P<0.01);肺癌组胸水三项指标高于血清水平(P<0.01);CEA对肺腺癌,NSE对小细胞肺癌,CYFRA21-1对肺鳞癌的阳性率高于其它单项(P<0.05)。结论:胸腔积液CEA、NSE、CYFRA21-1检测有助于肺癌的诊断。