Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, ≤2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, ≤5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, ≤36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, ≤10.0 ng/ml and ≤0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC. (Received May 8, 1997; accepted Oct. 30, 1997)     

Serum CYFRA 21-1 in cervical cancer patients treated with radiation therapy

Background: A fragment of cytokeratin 19, referred to as CYFRA 21-1, is abundant in the serum of many patients with malignant tumors and is recognized as one of the established tumor markers, especially for non-small-cell lung cancer. In this study, the clinical usefulness of CYFRA 21-1 was investigated in cervical cancer patients treated with radiation therapy with reference to squamous-cell-carcinoma-related antigen (SCC-Ag), a common tumor marker of cervical squamous cell carcinoma. Materials and methods: The serum levels of CYFRA 21-1 and SCC-Ag of 50 patients with squamous cell carcinoma of the uterine cervix were measured before and after radiation therapy. Results: CYFRA 21-1 was positive in 52% of the patients. The incidence increased with the stage of the cancer, and post-treatment increases were a sign of disease progression. During radiation, serum levels of CYFRA 21-1 decreased significantly and reflected the radiation effect well. In addition, CYFRA 21-1 was negative in all patients without distant metastasis at the end of radiation therapy. Compared with SCC-Ag, patients were less often positive for CYFRA 21-1, but there was a statistically positive correlation between the two markers (correlation matrix = 0.69). Conclusions: CYFRA 21-1 can be used in monitoring the outcome of patients with squamous cell carcinoma of the uterine cervix. It may be particularly useful for patients without SCC-Ag. Received: 8 September 1999 / Accepted: 22 December 1999     

血清CYFRA21—1在非小细胞肺癌诊断中的价值

本研究用酶免方法检测了66人血清CYFRA21—1水平,其中肺腺癌20例,肺鳞癌24例,小细胞肺癌(SCLC)10例,以12例肺良性疾病(BPD)为对照;同时检测了6例患者手术前后血清CYFRA21-1水平。结果:鳞癌组和腺癌组血清CYFRA21—1水平均明显高于SCLC组和BPD组;鳞癌组则明显高于腺癌组。不同病期非小细胞肺癌(NSCLC)血中CYFRA21—1水平也明显不同,Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期。6例患者血清CYFRA21—1水平术后均有明显下降。结果表明:血清CYFRA21—1水平对NSCLC特别是肺鳞癌有较高的特异性,在NSCLC特别是肺鳞癌的诊断和鉴别诊断有重要意义;治疗前后血清CYFRA21—1水平的变化有助于疗效的判断。     

Clinical significance of serum cytokeratin-19 fragment (CYFRA 21-1) in hepatocellular carcinoma

Background/Purpose

CYFRA 21-1, a soluble fragment of cytokeratin 19, is increased in serum in some patients with hepatocellular carcinoma, but the clinical significance of this increase is still unknown.

Methods

Serum concentrations of CYFRA 21-1 were measured in 240 patients with hepatocellular carcinoma prior to hepatic resection. The relationships between serum CYFRA 21-1 concentrations and clinicopathologic features were analyzed.

Results

The sensitivity of CYFRA 21-1 as a test for hepatocellular carcinoma was 18.8%. Serum CYFRA 21-1 was significantly higher in patients with portal vein tumor thrombus, and serum CYFRA 21-1 increased with the progression of portal vein tumor thrombus. Tumor size was related to serum CYFRA 21-1, but there were no significant correlations between serum CYFRA 21-1 concentrations and tumor differentiation or number of tumors. Although patients with stage IV tumor had significantly higher CYFRA 21-1 concentrations than those with stages I, II, and III, CYFRA 21-1 was not associated with postoperative prognosis.

Conclusions

Although high concentrations of CYFRA 21-1 were often detected in patients with a tumor diameter greater than 5?cm or tumor thrombus in the major portal vein, CYFRA 21-1 is not a useful diagnostic tool for hepatocellular carcinoma because of its low sensitivity.     

Clinical usefulness of CYFRA 21-1 for esophageal squamous cell carcinoma in radiation therapy

AIM: The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy. METHODS: Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy. RESULTS: CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome. CONCLUSIONS: The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.     

Diagnostic utility of CYFRA 21-1 in malignant pleural effusion

OBJECTIVE: The diagnostic utility of the tumour marker CYFRA 21-1 in malignant pleural effusion is not yet clear. This study was designed to evaluate the diagnostic utility of serum and pleural fluid CYFRA 21-1 in malignant pleural effusion. METHODOLOGY: The validity of serum and pleural fluid CYFRA 21-1 was determined in 62 patients with exudative pleural effusion (27 malignant and 35 benign). The diagnosis of malignant pleural effusion was defined by cytological or histological results. RESULTS: A statistically significant difference between the geometric means of CYFRA 21-1 levels in pleural fluid of benign and malignant aetiologies was observed (11.2 vs 63.3 ng/mL, P < 0.0001). In addition, there was a significant difference in the serum levels (0.95 vs 5.55 ng/mL, P < 0.0001). The sensitivity and specificity of pleural fluid CYFRA 21-1 in malignant pleural effusion, at the cut-off value of 55 ng/mL, was 74.1% and 97.1%, respectively. The sensitivity and specificity of serum CYFRA 21-1, at the cut-off value of 2.5 ng/mL, was 81.5% and 97.1%, respectively. Using a combination of serum and pleural fluid CYFRA 21-1 level, the sensitivity increased to 88.9%. CONCLUSION: Serum and pleural fluid CYFRA 21-1 are useful as measures in differentiating malignant from benign pleural effusion.     

支气管肺泡灌洗液和血清CEA、CYFRA21—1检测对肺癌诊断价值的研究

目的研究支气管肺泡灌洗液（BALF）和血清中癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA21—1）的检测在肺癌诊断中的价值。方法将近来在我院行纤维支气管镜检查的门诊或住院患者38例,分为2组,即肺癌组18例和肺良性病变组20例,纤支镜灌洗留取BALF和采集空腹血清,分别测定CEA、CYFRA21—1。结果肺癌组患者BALF和血清CEA、CY—FRA21-1的水平明显高于肺良性病变组,经比较有显著性差异（P〈0．01）;单个检测BALF和血清CEA、CYFRA21—1的敏感性为61．1％～72．2％,特异性65％～80％;联合检测BALF和血清CEA、CYFRA21—1的敏感性为44．4％～50．6％,较低,但特异性较高。为95％-100％,且准确性增加。结论BALF和血清CEA、CYFRA21—1的检测有助于肺癌的诊断,且支气管肺泡灌洗液CEA、CYFRA21—1的敏感性和特异性较血清高,联合检测能提高肺癌诊断的特异性和准确性。     

肝癌患者血清microRNA-21水平变化

目的：分析不同肝病患者血清microRNA-21（miR-21）水平,以探讨miR-21对肝细胞癌（HCC）的诊断价值。方法以实时定量逆转录PCR法检测正常人、慢性乙型肝炎（CHB）、肝硬化和HCC患者（各组均为25例）血清miR-21水平,分析miR-21水平与HCC临床病理学特征的关系。结果正常人、CHB和肝硬化患者血清miR-21相对水平分别为（1.1±1.7）、（2.3±2.6）和（2.8±2.5）,而HCC患者为（22.6±4.4）,显著高于前三组（P〈0.001）;HCC患者术后1w和1m血清miR-21相对水平分别为（18.4±3.5）和（3.1±2.7）,均较术前显著降低（P＜0.001）;HCC患者血清miR-21水平与肿瘤大小、癌栓以及HBV感染相关,与肿瘤分化程度、数目和血清AFP水平无相关性。结论 miR-21在HCC患者血清中显著升高,可能作为HCC早期诊断的潜在标志。     

血清HE4、NSE、CYFRA21-1水平变化对肺癌的诊断价值

目的探讨血清HE4、NSE、CYFRA21-1水平变化对肺癌的诊断价值。方法采用电化学发光法检测88例肺癌患者和70例肺良性疾病患者及50例健康对照者血清中的HE4、NSE、CYFRA21-1水平。结果肺癌组血清HE4、NSE、CYFRA21-1水平明显高于肺良性疾病组和健康对照组(P0.05);腺癌、鳞癌、小细胞肺癌分别以HE4、CYFRA21-1、N SE检测敏感性最高(P0.05);HE4、NSE、CYFRA21-1联合检测较单项检测诊断敏感性显著提高(P0.05)。结论 HE4、NSE、CYFRA21-1水平变化有助于肺癌的诊断和鉴别诊断,三项肿瘤标志物联合检测优于各项目单独检测。     

肝癌细胞不同制悬方法建立裸鼠移植瘤模型的比较

目的比较肝癌细胞不同制悬方法建立裸鼠皮下瘤及原位瘤模型,优选建模方法。方法将肝癌细胞分别采用PBS缓冲液(PBS组)、无血清DMEM溶液(DMEM组)和含10%血清的DMEM溶液(血清DMEM组)3种液体制悬后注入裸鼠皮下建立肝癌裸鼠皮下瘤模型,比较皮下瘤的体积、瘤重及成瘤率;将肝癌细胞分别采用PBS缓冲液(PBS组)、无血清DMEM溶液(DMEM组)和含10%血清的DMEM溶液(血清DMEM组)3种液体制悬后注入裸鼠肝脏建立肝癌裸鼠原位瘤模型,比较原位瘤的成瘤率。结果3组裸鼠皮下瘤模型的皮下瘤体积及瘤重相比,差异无统计学意义(P0.05),但是PBS组及DMEM组的成瘤率(90%和100%)明显高于血清DMEM组(40%),差异有统计学意义(P0.05);裸鼠原位瘤模型中PBS组的成瘤率(90%)明显高于DMEM组(40%)及血清DMEM组(20%),差异有统计学意义(P0.05)。结论采用PBS缓冲液或无血清DMEM溶液对肝癌细胞稀释制悬可以有效建立裸鼠皮下瘤模型,采用PBS缓冲液对肝癌细胞稀释制悬可以有效建立裸鼠原位瘤模型。     

人肝癌裸鼠移植模型的研究进展

肝癌的基础与临床研究迫切需要能真正模拟肝癌在人体内自然生长、侵袭及转移全部过程的动物模型.目前,人肝癌裸鼠移植模型是人体外最接近人类肝癌的整体实验模型,并且造模时间短,成功率高,按移植部位可以分为皮下移植、原位移植、腹腔移植以及转移模型.影响裸鼠移植模型建立的因素主要有人肝癌细胞或外科标本的特性、移植部位及移植癌细胞数量、裸鼠的品系和周龄以及生长环境和其他因素的影响.     

Circulating miR-21-5p level has limited prognostic value in patients with hepatocellular carcinoma and is influenced by renal function

BACKGROUNDMicroRNAs (miRNAs) have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma (HCC). Specifically, hsa-miR-21-5p (miR-21) is among the most frequently deregulated miRNA in cancer. The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue, mostly in the Asian population. Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p (miR-122), at present only limited knowledge is available for miR-21.AIMTo evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera.METHODSPatients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study. All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained. Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p. The results were compared to previously reported miR-122 data.RESULTSSurvival of HCC patients was comparable between patients with low and high serum miR-21 concentration. No association was observed between miR-21 level in sera and Child-Pugh score, Barcelona Clinic Liver Cancer staging system, or etiology of HCC/liver disease. Age, gender, or pretreatment had no association with miR-21 level. A positive correlation was observed between miR-21 and aspartate aminotransferase (r = 0.2854, P = 0.0061), serum miR-122 (r = 0.2624, P = 0.0120), and the International Normalized Ratio (r = 0.2065, P = 0.0496). Negative correlation of miR-21 with serum creatinine (r = -0.2215, P = 0.0348) suggests renal function as a potential influencing factor in miR-21 biogenesis in blood.CONCLUSIONThe results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings. Following systematic evaluation, we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood. This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.     

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.     

血清细胞角蛋白19片段检测对肺癌的临床意义

目的确定我国肺癌患者血清细胞角蛋白１９片段（ＣＹＦＲＡ２１－１）浓度阈值，探讨其临床应用价值。方法应用单克隆抗体（Ｋｓ１９．１和ＢＭ１９．２１）检测７２例初次确诊肺癌患者和５０例肺良性疾病患者以及３３例治疗后肺癌患者血清ＣＹＦＲＡ２１－１水平。采用ＲＯＣ曲线确定ＣＹＦＲＡ２１－１浓度阈值。结果（１）肺癌患者血清ＣＹＦＲＡ２１－１水平显著高于肺良性疾病患者（Ｐ＜０．００１），鳞癌显著高于其它病理类型，且其浓度随临床分期升高而升高。（２）当阈值定为５．５μｇ／Ｌ时，ＣＹＦＲＡ２１－１检测肺癌的敏感性、特异性分别为６３％和９４％。鳞癌敏感性最高为７８％。（３）ＣＹＦＲＡ２１－１检测非小细胞肺癌的敏感性随临床分期升高而升高。（４）ＣＹＦＲＡ２１－１是监测肺癌病情、提示疗效的良好指标。（５）当ＣＹＦＲＡ２１－１作为筛检肺癌的指标时，阈值宜取非小细胞肺癌Ｉ－ＩＩ期ＲＯＣ曲线拐点，但对非小细胞肺癌早期诊断作用有限。结论ＣＹＦＲＡ２１－１是一较好的非小细胞肺癌肿瘤标记物，尤其适用于肺鳞癌     

肝癌细胞转移与PI3K-Akt-PAK1通路的相关性研究

目的 研究肝细胞癌（HCC）组织PI3K/Akt/ p21活化蛋白激酶1（PAK1）信号通路的表达对于HCC发生及转移的重要性,以期为HCC的预防和预后提供一个有效的分子标志,并为HCC的治疗提供一定的理论基础。方法 自NCBI中GEO数据库中的GES364数据集提取数据,对PI3K/Akt/PAK1信号通路基因的表达量进行分析。结果 将数据库中HCC组织分为肝内扩散组（PS）、肝外转移组（PM）、无转移组（PN）和正常肝对照组（H）。分析发现PS组和PM组PAK1和MMP-9表达量明显高于H组和PN组（P<0.0001）;PS组、PM组和PN组AKT（1/2）和Girdin表达量明显高于H组（P<0.05）,PS组和PM组AKT2和Girdin表达量也明显高于PN组（P<0.05）;在PM组,AKT2与PAK1表达呈正相关（r=0.5679,P=0.0013）。结论 PAK1和MMP-9高表达可以促进HCC的扩散和转移,而AKT的表达和活性对于HCC的转移也是至关重要的,提示PI3K/AKT/PAK1信号通路与HCC转移密切相关。     

CYFRA 21-1对非小细胞肺癌胸腔积液的诊断价值

目的　探讨非小细胞肺癌标记物 (CYFRA 2 1- 1)对非小细胞肺癌 (NSCLC)胸腔积液的诊断价值。方法　用放免法测定了非小细胞肺癌 ,小细胞肺癌 (SCLC)及结核性胸膜炎的胸腔积液CYFRA 2 1- 1水平。结果　非小细胞肺癌胸腔积液的CYFRA 2 1- 1水平 ,无论细胞学阳性或阴性 ,均显著高于小细胞肺癌及结核性胸膜炎的胸腔积液组 (P <0 0 1)。结论　检测胸腔积液CYFRA 2 1- 1对非小细胞肺癌胸腔积液的诊断有重要价值     

High level of intercellular adhesion molecule-1 affects prognosis of patients with hepatocellular carcinoma

AIM: To determine the cut-off value of intercellular adhesion molecule-1 (ICAM-1) and assess the correlation of ICAM-1 with clinicopathological features and the prognosis of hepatocellular carcinoma (HCC) patients who underwent surgical resection.METHODS: We prospectively collected clinicopathological data from 236 HCC patients who had undergone successful hepatectomy. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of ICAM-1. Enzyme-linked immunosorbent assay was used to measure the concentration of ICAM-1 in 236 serum samples isolated from HCC patients and the stratified analysis was used to compare the serum level of ICAM-1 in different HCC subgroups. Immunohistochemistry was performed to test the expression level of the ICAM-1 protein in 76 cases of HCC tissues and their adjacent normal liver tissues (ANLT). The survival probability of HCC patients was estimated using Kaplan-Meier plots and differences between the groups were obtained using the log-rank test. Furthermore, independent indicators of the prognosis were acquired using a stepwise Cox proportional hazard model to analyze a series of predictors that were associated with disease-free survival (DFS) and overall survival (OS) in HCC patients.RESULTS: Our findings suggested that ICAM-1 promotes HCC metastasis and high serum ICAM-1 is significantly associated with alpha-fetoprotein (AFP) (P = 0.022), clinical tumor-node-metastasis stage (P < 0.001), portal vein tumor thrombus (P = 0.005), distant metastasis (P = 0.016) and recurrence (P = 0.034). We further detected the ICAM-1 protein in HCC specimens and found that 56 of 76 (73.7%) HCC tissues had ICAM-1 positive staining while only 23 of 76 (30.3%) ANLT were positively stained (P < 0.0001). Survival analysis indicated that HCC patients with increased ICAM-1 concentrations had significantly shorter DFS and OS after resection. A multivariate analysis showed that ICAM-1 > 684 ng/mL was an independent factor for DFS (HR = 1.643; 95%CI: 1.125-2.401; P = 0.010) and OS (HR = 1.692; 95%CI: 1.152-2.486; P = 0.007).CONCLUSION: ICAM-1 may be a promising serological biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection and may provide a useful reference for the prediction of intra- and extrahepatic metastasis.     

老年2型糖尿病患者HbA1c与CYFRA21-1、CA199水平的相关性分析

目的 探讨老年2型糖尿病(T2DM)患者HbA1c和CYFRA21-1、CA199水平的相关性.方法 选取60例老年T2DM患者和60例中年T2DM患者,所有患者治疗时间处于2018年1月—2019年1月,根据患者患者糖化血红蛋白(HbAlc)水平,以7.0％为标准界限,HbAlc<7.0％的为血糖良好组,HbAlc>...     

细胞角质片段21-1、神经元特异性烯醇化酶在肺癌早期诊断中应用价值的探讨

目的　评价肿瘤标记物细胞角质片段 2 1 1(CYFRA2 1 1)、神经元特异性烯醇化酶(NSE)对肺癌早期诊断的价值。方法　将 3 0例肺癌患者分为非小细胞性肺癌组 (NSCLC)和小细胞性肺癌组 (SCLC) ,良性疾病患者为对照组。所有患者均经支气管镜检查进行患侧和健侧肺泡灌洗 ,收集肺泡灌洗液 (BALF) ,同时采静脉血 ,按放射免疫方法 (RIA)检测CYFRA2 1 1、NSE。结果　CYFRA2 1 1水平在NSCLC中明显高于SCLC和良性疾病患者。NSE则在SCLC中显著高于NSCLC和良性疾病组。各组BALF中CYFRA2 1 1、NSE水平均以患侧增高明显 (P <0 .0 5或0 .0 1) ,CYFRA2 1 1、NSE联合检测与各单项指标相比 ,正确率提高 ,以患侧BALF联合检测方法最优。结论　联合检测患侧BALF中CYFRA2 1 1、NSE的含量诊断肺癌的阳性率最高 ,准确性达97.14 %。