肺癌患者异常糖链糖蛋白与传统肿瘤标志物的相关性分析

目的通过回顾性分析肺癌患者异常糖链糖蛋白(TAP)水平以及传统肿瘤标志物癌胚抗原(CEA)、鳞状细胞癌抗原(SCC)、糖类抗原125(CA125)、神经元特异性烯醇化酶(NSE)和细胞角蛋白19片段(CYFRA21-1)水平,探讨肺癌患者TAP与传统肿瘤标志物之间的相互关系。 方法分别采用凝聚素亲和法及电化学发光免疫分析法检测我院呼吸内科经治的181例肺癌患者TAP和5种血清学肿瘤标志物的水平,对所得TAP与5种血清学肿瘤标志物的数据进行spearman相关性检验分析。 结果肺癌患者TAP与CEA呈正相关(P＝0.016),而与SCC、CA125、NSE及CYFRA21-1之间没有相关性(P值均>0.05);亚组分析,腺癌、鳞癌患者的TAP与CEA均呈正相关(P值分别为0.021,0.044),腺癌、鳞癌、小细胞癌及未分类癌患者的TAP与CA125均呈正相关(P值分别0.046,0.007,0.001,0.006),而这四类癌的TAP与SCC、NSE和CYFRA21-1之间没有明显相关性(P值均>0.05)。 结论肺癌患者TAP值是CEA、CA125等多种肿瘤异常蛋白水平的综合体现,尤其在肺腺癌患者中与传统肿瘤标志物具有较好的正相关性。     

Factors that predict progression-free survival in Chinese lung adenocarcinoma patients treated with epidermal growth factor receptor tyrosine kinase inhibitors

Background

Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown efficacy in patients with advanced lung cancers, survival predictors with these drugs have not been extensively investigated. This study was performed to explore factors that may predict progression-free survival (PFS) in Chinese lung adenocarcinoma patients treated with EGFR-TKIs.

Methods

We retrospectively collected clinicopathologic data on 208 patients who received either gefitinib, erlotinib or icotinib, including the patients’ EGFR mutation status and levels of six serum tumor markers [carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCC), cytokeratin-19 fragments (CYFRA21-1) and lactate dehydrogenase (LDH)]. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with PFS.

Results

At the study cutoff date, 189 (90.9%) of the patients met the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 criteria for progressive disease (PD), while 19 (9.1%) had stable disease (SD). The median PFS of the 208 patients was 12.4 months (95% CI, 11.0–13.8 months). In the multivariate analysis using a Cox proportional hazard model, a non-smoking history [hazard ratio (HR) =2.460; 95% CI, 1.484–4.079; P<0.001], first-line treatment (HR =1.500; 95% CI, 1.062–2.119; P=0.021), and a high pretreatment serum level of CEA (HR =1.424; 95% CI 1.026–1.977; P=0.035) were found to be significant predictors of a longer PFS.

Conclusions

In Chinese lung adenocarcinoma patients treated with EGFR-TKIs, a non-smoking history, first-line EGFR-TKIs treatment and a high serum level of CEA were independent predictors of a longer PFS along with an EGFR-activating mutation.     

血清肿瘤标志物与肺癌的关系

目的探讨血清肿瘤标志物与肺癌的关系；方法取确诊肺癌患者治疗前后血清测定CEA、CAl25、NSE、CYFRA21—1、AFP、CA19-9、CAl5-3、CA724、SCC；与非肺癌患者对照，采用多组均数的非参数检验（krus—wallis检验）、T检验；结果在腺癌患者CEA、CA15-3水平最高；NSE、CA19-9在小细胞癌患者水平最高；CYFRA21—1在鳞癌最高；CA724在大细胞癌中最高（P〈0．01）；与非肺癌患者具有显著差异的是CEA、NSE、CYFRA21—1、CA19-9、CA15-3、CA724（P〈0．01）。血清肿瘤标志物治疗前后差异没有显著性；结论血清肿瘤标志物CEA、CA15-3、NSE、CA19-9、CYFRA21—1、CA724对一些肺癌的诊断有意义。     

肺癌患者自身抗体与肿瘤标志物相关性分析

目的探讨肺癌自身抗体与肿瘤标志物之间的相互关系。方法收集2016年9月至2016年12月收治于第四军医大学唐都医院呼吸内科的肺癌患者112例,分别采用酶联免疫吸附实验法和电化学发光免疫分析法检测肺癌患者7种自身抗体和5种血清学肿瘤标志物的水平,对所得患者自身抗体P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGE和CAGE,以及肿瘤标志物CEA、SCC、CA125、NSE和CYFRA21-1,的数据进行spearman相关性检验分析。结果不同病理类型肺癌患者的自身抗体水平,肺腺癌患者GAGE7中位数为7.30 U/ml,明显高于鳞癌、小细胞癌等其他类型的肺癌患者(P=0.041),而P53、PGP9.5、SOX2、GBU4-5、MAGE和CAGE水平则无统计学差异。传统的肿瘤标志物CEA和CA125在肺腺癌中、SCC在肺鳞癌中明显升高(P值均0.05)。经spearman相关性检验分析,在肺癌中,P53与CEA、SCC呈正相关(P值分别为0.024,0.016),PGP9.5与NSE呈正相关(P0.001),GBU4-5与SCC、CA199呈正相关(P值分别0.001,=0.011),MAGE与SCC、CA199呈正相关(P值分别=0.004,0.001)。结论肺癌患者自身抗体与肿瘤标志物存在正相关,同时检测二者可相互补充,更益于肺癌的及时诊断。     

Expression and prognostic relevance of tumor carcinoembryonic antigen in stage IB non-small cell lung cancer

Background

High serum carcinoembryonic antigen (CEA) levels have been reported to be associated with poor prognosis in non-small cell lung cancer (NSCLC), while the prognostic role of tumor CEA expression remains to be defined. The present study investigated the expression of tumor CEA in stage IB NSCLC, and correlated it with clinicopathological features and prognosis.

Patients and methods

Immunohistochemistry for tumor CEA was assessed in the specimens of 183 patients with stage IB NSCLC. Receiver-operating characteristic (ROC) curve analysis was used to determine the cut-off score for tumor positivity.

Results

High CEA expression was detected more frequently in adenocarcinomas (72.2%) and other NSCLCs (69.0%) than in squamous cell carcinomas (25.4%, P<0.001). Both univariate and multivariate analysis indicated that tumor CEA was an independent prognostic factor for overall and disease-free survival (P<0.05).

Conclusions

Elevated expression of tumor CEA may be an adverse prognostic indicator in stages IB NSCLC.KEY WORDS : Non-small cell lung cancer, carcinoembryonic antigen, prognosis, receiver operating characteristic curve     

肺癌患者血清和胸水中常用肿瘤标志物的检测

目的探讨肺癌患者血清和胸水中6种肿瘤标志物的检测意义，并选择较理想的肿瘤标志物组合。方法应用ELISA检测120例肺癌患者和90例肺部良性疾病患者血清和胸水中以及50例健康人血清中神经元特异性烯醇化酶（NSE）、胃泌素释放肽前体（pro-GRP）、细胞角质蛋白19（CYFRA21-1）、鳞癌抗原（SCC）、p53抗体和癌胚抗原（CEA）的水平含量。结果肺癌患者血清和胸水6种肿瘤标志物水平均明显高于健康人组和肺部良性疾病组（P〈0．01）。肺部良性疾病组胸水中NSE、CYFRA21—1和CEA的假阳性率较高。血清NSE、pro—GRP在小细胞肺癌中的水平和敏感性明显高于其他类型的肺癌（P〈0．01）；血清CYFRA21-1、SCC在肺鳞癌中的水平和敏感性明显高于其他类型的肺癌（P〈0．01）。6种血清肿瘤标志物经组合后，在特异性下降不大的情况下。敏感性明显高于任一单项肿瘤标志物（P〈0．01）。结论6种肿瘤标志物的检测对于肺癌的辅助诊断有一定的临床意义。血清NSE、pro-GRP可作为联合检测小细胞肺癌的标志物组合；血清CYFRA21-1、SCC可作为联合检测肺鳞癌的标志物组合；血清NSE、CYFRA21-1、CEA可作为联合检测非小细胞肺癌的标志物组合。     

Prognostic value of serum tumor markers in patients with lung cancer

BACKGROUND: The role of tumor markers in the diagnosis and prognosis of lung cancer is under investigation. OBJECTIVES: The aim of this study was to investigate the diagnostic and prognostic significance of pre-therapeutic levels of various serum tumor markers, CYFRA 21-1, neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), CA 125 and squamous cell carcinoma antigen (SCCAg), in patients with lung cancer. METHODS: We studied 102 consecutive patients (mean age 65.2 +/- 11 years) with newly diagnosed lung cancer (96 males, 94%, with a mean age of 66.3 +/-10.5 years). All patients had a 5-year follow-up. Measurements of the serum tumor markers were performed on initial diagnosis. RESULTS: Eighty-four patients (82%) had non-small-cell lung cancer (NSCLC) and 18 (18%) small-cell lung cancer (SCLC). From the 84 patients with NSCLC, 34 patients (33%) had squamous-cell lung cancer, 23 (22%) adenocarcinoma and 23 (22%) large-cell carcinomas. The overall median survival was 8.5 months. All SCLC patients had extensive disease with a median survival of 10.1 months and NSCLC patients of 8.4 months. Significant differences in the mean values of NSE and CYFRA 21-1 were observed between SCLC and NSCLC. In NSCLC, CYFRA 21-1, TPA, CA 125 and SCCAg serum levels were related to the stage of the disease at diagnosis, and CYFRA 21-1, NSE, TPA and CA-125 were related to a poor outcome. None of the above tumor markers was related to survival in the SCLC group. CONCLUSION: CYFRA 21-1 and NSE may help to differentiate cell types in lung cancer patients. Also, CYFRA 21-1 with TPA and CA 125 may provide useful information regarding the staging of the disease at diagnosis and the prognosis of patients with NSCLC.     

肺泡灌洗液和血清中肿瘤标志物检测在肺癌诊断中的价值

目的探讨支气管肺泡灌洗液与血清中肿瘤标志物检测在肺癌的临床诊断价值。方法测定患者支气管肺泡灌洗液与血清中的癌胚抗原(CEA)、鳞状细胞癌相关抗原(SCC)和神经元特异性烯醇化酶(NSE)以及可溶性细胞角蛋白19片段(CYFRA21-1)的含量。结果研究组血清和支气管肺泡灌洗液中CEA、SCC和NSE以及CYFRA21-1含量均明显高于对照组(P0.05)。支气管肺泡灌洗液与血清中不同病理类型和不同临床分期患者的CEA、SCC和NSE以及CYFRA21-1比较有统计学意义(P0.05)。结论检测支气管肺泡灌洗液中的肿瘤标志物对肺癌的诊断效果明显的由于检测血清中的肿瘤标志物诊断效果,对患者的病情程度和预后均具有一定的临床应用价值。     

肺癌中CYFRA21—1、SCC、NSE的表达及预后研究

目的研究肺癌相关的血清细胞角蛋白片断21-1（CYFRA21-1）、鳞状上皮细胞癌抗原（SCC）和神经特异性烯醇化酶（NSE）3种肿瘤标志的临床应用价值。方法采用化学发光法,放免法。采取静脉血,分别检测38例肺癌患者,44例肺良性疾病患者成人血清中的CYFRA21-1、SCC和NSE的表达,并对所有的患者进行随访检测。同时用SPSS10．0统计软件分析,评价肿瘤标志物的临床应用价值。结果血清CYFRA21—1、SCC和NSE水平随临床分期（TNM）增加而升高,与肺良性疾病比较差异有显著性（P〈0．01）,对于评价肺癌具有一定的临床参考价值。在检测中,以CYRA21—1、SCC和NSE联合检测敏感性和有效性最高。对于肺癌与肺良性疾病的鉴别具有一定的参考价值,经化疗加岩舒使肿瘤进展时间延长并延长生存期。结论3种肿瘤标志物在肺癌诊断、鉴别诊断和治疗中,具有一定的临床应用价值。     

Elevated expression of USP9X correlates with poor prognosis in human non-small cell lung cancer

Background

The aim of this study was to investigate the expression of ubiquitin-specific peptidase 9, X-linked (USP9X) in non-small cell lung cancer (NSCLC) patients and to evaluate the relevance of USP9X expression to tumor prognosis.

Methods

Ninety-five patients who underwent surgical resection for clinical stage I-IIIA NSCLC between July 2008 and July 2011 were included in this study. Immunohistochemical analysis of USP9X expression was performed on 95 NSCLC tissues and 32 adjacent normal lung parenchymal tissues from these patients. The Chi-squared test was used to compare the clinicopathological characteristics between different groups. Kaplan-Meier analysis and a Cox regression model were used to determine the independent prognostic factors. A P value <0.05 was considered to be significant.

Results

The expression of USP9X was found to be significantly higher in NSCLC tissue (44.2%) than in adjacent normal lung parenchymal tissue (6.3%) (P<0.001). High USP9X expression was significantly associated with positive lymph node metastasis (P<0.001), clinical stage (P<0.001) and a reduced overall survival rate (P=0.001) in patients with NSCLC. Based on the multivariate analysis, the elevated expression of the USP9X protein was a significant predictor of poor prognosis for NSCLC patients (HR =2.244, P=0.028).

Conclusions

The current study demonstrated that the expression of USP9X in NSCLC tissue was significantly higher than that in normal lung tissue and that this elevated expression level of USP9X was associated with poor prognosis among NSCLC patients, suggesting that USP9X might serve as a prognostic biomarker for NSCLC.     

Tumor markers in pleural effusion of patients with lung cancer and patients with tuberculous pleurisy]

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), NCC-ST-439, carbohydrate antigen 19-9 (CA 19-9), cytokeratin 19 fragment (CYFRA 21-1), sialyl Lewis X-i antigen (SLX), progastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) were evaluated in the pleural effusion of 39 patients with lung cancer (29 adenocarcinomas, seven small-cell carcinomas, three squamous cell carcinomas) and 43 patients with tuberculous pleurisy. The levels of the tumor markers other than SCC and NSE were significantly higher in lung cancer than in tuberculosis. High levels of CYFRA 21-1 and SCC were observed in squamous cell carcinoma and high levels of ProGRP and NSE were observed in small-cell carcinoma. According to the validity score, sensitivity (%) + specificity (%) - 100, the optimal cut-off levels of pleural effusion were 8.1 ng/ml for CEA, 660 U/ml for CA 125, 2.6 U/ml for NCC-ST-439, 10 U/ml for CA 19-9, 65 ng/ml for CYFRA 21-1, 140 U/ml for SLX, 23.2 pg/ml for ProGRP, 0.6 ng/ml for SCC and 5 ng/ml for NSE. By comparison of validity scores for each optimal cut-off level and of receiver operating characteristic (ROC) curves, we suggest that a CEA assay is the most useful for pleural effusion. The combined assay of CEA + ProGRP and CEA + ProGRP + CYFRA 21-1 were considered to be useful.     

Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma

Background

Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy.

Methods

Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining.

Results

A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers.

Conclusions

The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data.     

The association of topoisomerase 2α expression with prognosis in surgically resected non-small cell lung cancer (NSCLC) patients

Background

Topoisomerase 2α (Topo 2α) is a nuclear enzyme that alters the topology of DNA. It’s essential for normal chromosome segregation during cellular division. We aimed to investigate the association of Topo 2α expression with clinical, pathological parameters and prognosis in surgically resected non-small cell lung cancer (NSCLC) patients.

Methods

The study is comprised of 100 surgically resected NSCLC (squamous cell carcinoma in 50 patients, adenocarcinoma in 50 patients). The paraffin embedded tumor sections were retrieved for expression of Topo 2α. Nuclear and cytoplasmic expression of Topo 2α was determined by immunohistochemistry. Clinical, pathological data and survival of patients were determined from the hospital files. Median follow-up time was 35 (range, 4-120) months.

Results

Nuclear and cytoplasmic expression of Topo 2α was positive in 41 (41%) and 66 (66%) patients, respectively. There was no significant association between nuclear or cytoplasmic expression of Topo 2α and age, gender, smoking history. While nuclear expression was significantly increased in squamous cell carcinoma (P=0.008), OR (95% CI): 3.01 (1.31-6.92), cytoplasmic expression wasn’t different. Both nuclear and cytoplasmic expression didn’t show any association with tumor diameter, pathological stage, tumor differentiation and relapse. There was no significant association between nuclear or cytoplasmic expression of Topo 2α and survival. Tumor diameter (P=0.031) and metastasis to N2 lymph nodes (P=0.005) were independent prognostic factors.

Conclusions

There was no association between Topo 2α expression and prognosis in surgically resected NSCLC patients. Nuclear expression of Topo 2α was significantly higher in patients with squamous cell carcinoma.Key Words : Non-small cell lung cancer, topoisomerase 2α, prognosis     

miR-132 inhibits lung cancer cell migration and invasion by targeting SOX4

Background

Multiple MicroRNAs (miRNAs) have been identified in the development and progression of lung cancer. However, the expression and roles of miR-132 in non-small cell lung cancer (NSCLC) remain largely undefined. The aim of this study is to investigate the biological functions and its molecular mechanisms of miR-132 in human lung cancer cells.

Methods

miR-132 expression was measured in human lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The cells migration and invasion ability were measured by wound healing assay and transwell assay. The influence of miR-132 on tumor progression in vivo was monitored using NSCLC xenografts in nude mice. The target gene of miR-132 was determined by luciferase assay and western blot.

Results

The expression level of miR-132 was dramatically decreased in examined lung cancer cell lines. Then, we found that introduction of miR-132 significantly suppressed the migration and invasion of lung cancer cells in vitro. Besides, miR-132 overexpression could also inhibit tumor growth in the nude mice. Further studies indicated that the sex determining region Y-box 4 (SOX4) is a target gene of miR-132. SOX4 re-introduction could reverse the anti-invasion role of miR-132.

Conclusions

Our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-132 may serve as a potential target in the treatment of human lung cancer.     

Surgical specimen histology revealed inadequacy of conventional transbronchial needle aspiration sample in the diagnosis of adenosquamous lung carcinoma

Objective

We retrospectively reviewed the accuracy of conventional transbronchial needle aspiration (cTBNA) in the subtyping of lesions located in or around central airways by comparing the histological diagnosis based on TBNA and surgical specimens.

Materials and methods

cTBNA was conducted in consecutive patients with lesions located in or around the central airways (trachea, left and right primary bronchi, hilar and mediastinal masses or lymph nodes) between October 2012 and May 2014 in Wuhan No. 1 Hospital. The aspirated specimens in all patients were performed cytological and/or histopathological examination. Of these patients, some were subjected to surgical resection and histopathological examination was performed by the Department of Pathology. In the patients with gross specimens, the final diagnosis was established based on histopathological results from these specimens.

Results

In 63 patients diagnosed with cTBNA for the lesions located in or around the central airways, 23 patients with a diagnosis of lung cancer or atypical hyperplasia underwent surgery. The final diagnosis based on histopathology of surgery specimen was lung cancer in 22 patients [3 small cell lung cancer (SCLC), 9 squamous cell carcinoma (SCC), 5 adenocarcinoma (ADC), 4 adenosquamous carcinoma (ADS) and 1 neuroendocrine carcinoma], and inflammatory pseudotumor in 1 patient. The overall diagnostic yield of cTBNA for lung cancer was 95.7% (22/23), but the accuracy for histological typing of lung cancer is only 63.6% (14/22), for adenosquamous lung carcinoma was only 25% (1/4).

Conclusions

cTBNA is a safe and effective procedure that can be used for the diagnosis of central lung cancer. However, the accuracy of TBNA for the histological classification of lung cancer is relatively low, especially for adenosquamous lung carcinoma.     

miR-1290 is a potential prognostic biomarker in non-small cell lung cancer

Background

miR-1290 is a newly discovered microRNA (miRNA), and its role in non-small cell lung cancer (NSCLC) remains unknown. This study aimed to evaluate the expression levels of miR-1290 in NSCLC tissues and serum, and explore its associations with clinicopathological characteristics and prognosis of NSCLC patients.

Methods

A total of 33 pairs of tissues and 73 serum samples were obtained from NSCLC patients and expression levels of miR-1290 were detected by specific TaqMan qRT-PCR. The relationship between miR-1290 expression levels in NSCLC tissues and serum and clinicopathological characteristics was estimated respectively. The correlation between serum miR-1290 expression levels and overall survival of NSCLC patients was performed by Kaplan-Meier analysis and Cox proportional hazards model.

Results

We determined that miR-1290 expression levels were increased significantly in NSCLC tissues compared with non-tumor adjacent normal tissues, and higher miR-1290 expression levels were positively correlated with high tumor stage (P=0.004) and positive lymph node metastasis (P=0.013). Compared with benign lung disease and healthy controls, serum levels of NSCLC patients exhibited higher expression of miR-1290. Furthermore, the up-regulation of serum miR-1290 more frequently occurred in NSCLC patients with high TNM stage, positive lymph node metastasis (P=0.022 and P=0.024, respectively). Kaplan-Meier analysis demonstrated that high serum miR-1290 expression levels predicted poor survival (P=0.022). Cox proportional hazards risk analysis indicated that miR-1290 was an independent prognostic factor for NSCLC.

Conclusions

Our study suggests that miR-1290 is overexpressed in NSCLC, and serum miR-1290 may be used as a potential prognostic biomarker for NSCLC.     

四种肿瘤标志物血清水平的联合检测对肺癌诊断的临床价值

目的探讨血清肿瘤标志物细胞角蛋白19片段（CYFRA21-1）、神经元特异性烯醇化酶（NSE）、癌胚抗原（CEA）、糖类抗原125（CA125）联合检测对肺癌诊断的临床价值。方法采用瑞士罗氏公司cobas e 411型全自动电化学发光免疫分析系统检测经病理确诊的52例肺癌患者、30例肺部良性疾病患者及35例正常人血清CYFRA21-1、NSE、CEA、CA125水平,并计算阳性率、特异度及准确度。结果肺癌组血清4种肿瘤标志物水平显著高于肺良性疾病及健康对照组。其中单项检测CYFRA21-1阳性率以鳞癌最高（70.8%）,NSE阳性率以小细胞肺癌最高（75.0%）,CEA阳性率以腺癌最高（65.0%）,与其他型肺癌相比差异有统计意义。4种肿瘤标志物联合检测阳性率、特异度及准确度明显高于单项检测结果。结论 4种肿瘤标志物对于肺癌的辅助诊断均具有实用价值,且联合检测有助于提高肺癌诊断的阳性率、特异度及准确度。     

肺癌患者血清肿瘤标志物水平变化与化疗疗效及生存时间的相关性

目的探讨晚期肺癌患者化疗前后血清癌胚抗原（CEA）、细胞角质蛋白（CYFRA21-1）、鳞状细胞癌抗原（SCC）和神经烯醇化酶（NSE）水平变化与化疗疗效及生存时间的相关性。方法分别采集2006年1月至2012年6月确诊肺癌（Ⅲb-Ⅳ期）116例患者的化疗前及四疗程化疗后的血清标本,检测每份标本CEA、CYFRA21-1、SCC和NSE四种肿瘤标记物水平,探讨它们之间的差值差异及与化疗效果和生存时间的关系。结果四疗程化疗有效及进展的患者中位生存时间为16个月及9个月;结合生存曲线显示化疗有效的晚期肺癌患者较进展者生存时间更长。化疗前后肿瘤标志物水平变化与化疗疗效密切相关。化疗有效者相应肿瘤标志物下降;进展者标志物上升。其中不同疗效组的鳞癌患者CYFRA21-1及SCC水平,腺癌患者CEA水平,小细胞癌患者CEA及NSE差值差异明显（P〈0．05）。通过比较不同生存时间组的患者化疗前后肿瘤标志物的差值差异发现患者生存时间越长,化疗后相应的肿瘤标志物下降幅度越大;生存时间越短标志物上升越明显。其中鳞癌患者CYFRA21—1及SCC,腺癌患者CEA和小细胞癌患者CEA及NSE指标变化有统计学意义。结论CEA、CYFRA21—1,SCC和NSE这四种肿瘤标志物化疗前后差值可作为反映化疗疗效及评估一年生存时间的重要指标,且具有病理类型的特异性。     

Egy-Score Predicts Severe Hepatic Fibrosis and Cirrhosis in Egyptians With Chronic Liver Diseases: A Pilot Study

Background

Non-invasive methods for assessment of hepatic fibrosis are increasingly needed. Recent studies showed that combined elevation of tumor markers CA 19-9 and CA 125 is predictive of severe hepatic fibrosis or cirrhosis with high specificity.

Objectives

We aimed at developing a new panel of surrogate biomarkers for prediction of the stage of hepatic fibrosis by combining tumor markers with other known biomarkers of hepatic fibrosis.

Patients and Methods

A total of 92 patients with different types of chronic liver diseases (chronic hepatitis B, chronic hepatitis C and autoimmune hepatitis), were prospectively enrolled in our cohort. They were subjected to: ALT, AST, GGT, ALP, total bilirubin, INR, total cholesterol, albumin, platelet count, cancer antigen 19-9 (CA 19-9), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), haptoglobin, alpha-2-macroglobulin, apolipoprotein A1, abdominal ultrasound, liver biopsy and histological staging of hepatic fibrosis using the METAVIR system.

Results

Combined elevation of CA 19-9 and CA 125 with a summated value > 37 U/mL is predictive of severe hepatic fibrosis or cirrhosis (stage F3-F4 METAVIR) with a probability of 77.6%. Multivariate analysis showed that the most relevant collection of biomarkers for prediction of stage of hepatic fibrosis is: CA 19-9, age, alpha-2- macroglobulin, total bilirubin, platelet count & albumin. We developed a new score, named the “Egy-Score”, using a regression equation composed of this panel of biomarkers. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3-F4 METAVIR) with 83.7% accuracy.

Conclusions

Non-invasive assessment of hepatic fibrosis could be done using the Egy-Score. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3 - F4 METAVIR) with 83.7% accuracy.