Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseases

The current best serum marker for pancreatic cancer, CA 19-9, detects a carbohydrate antigen on multiple protein carriers. Better knowledge of the protein carriers of the CA 19-9 antigen in various disease states may lead to improved diagnostic tests. To identify proteins that carry the CA 19-9 antigen, we immunoprecipitated the CA 19-9 antigen from pooled sera and identified the associated proteins using MS. Among the high-confidence identifications, we confirmed the presence of the CA 19-9 antigen on Apolipoprotein B-100 by antibody arrays and Western blot and on kininogen, ARVCF, and Apolipoprotein E by antibody arrays. We characterized the frequency and levels of the CA 19-9 antigen on the four proteins across various patient groups (pancreatic cancer, pancreatitis, and healthy controls) using antibody arrays. Nearly, 10-25% of the subjects showed elevations of the antigen on each protein, but the elevations were not associated with disease state or total CA 19-9 levels. These results contribute to our knowledge of the carrier proteins of an important functional glycan and the rate at which the glycan is displayed. This work also demonstrates a strategy for using the complementary methods of MS and antibody microarrays to identify protein carriers of glycans and assess the diagnostic value of measuring glycans on individual proteins.     

Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation

The CA 19-9 antigen is currently the best individual marker for the detection of pancreatic cancer. In order to optimize the CA 19-9 assay and to develop approaches to further improve cancer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9 antibodies used in the analysis of plasma samples from pancreatic cancer patients and controls. Major differences were observed between antibodies in their detection of particular patient samples. Glycan array analysis revealed that certain antibodies were highly specific for the canonical CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to a related structure called sialyl-Lewis C and modification with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C glycan by one of the antibodies and showed that the broader specificity led to the detection of an increased number of cancer patients without increasing detection of pancreatitis patient samples. This work demonstrates that variation between antibody specificity for cancer-associated glycans can have significant implications for biomarker performance and highlights the value of characterizing and detecting the range of glycan structures that are elevated in cancer.     

Comprehensive proteomic analysis of human pancreatic juice

Proteomic technologies provide an excellent means for analysis of body fluids for cataloging protein constituents and identifying biomarkers for early detection of cancers. The biomarkers currently available for pancreatic cancer, such as CA19-9, lack adequate sensitivity and specificity contributing to late diagnosis of this deadly disease. In this study, we carried out a comprehensive characterization of the "pancreatic juice proteome" in patients with pancreatic adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel electrophoresis and subsequently analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 170 unique proteins were identified including known pancreatic cancer tumor markers (e.g., CEA, MUC1) and proteins overexpressed in pancreatic cancers (e.g., hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) and lipocalin 2). In addition, we identified a number of proteins that have not been previously described in pancreatic juice (e.g., tumor rejection antigen (pg96) and azurocidin). Interestingly, a novel protein that is 85% identical to HIP/PAP was identified, which we have designated as PAP-2. The proteins identified in this study could be directly assessed for their potential as biomarkers for pancreatic cancer by quantitative proteomics methods or immunoassays.     

Carbohydrate markers of pancreatic cancer

Pancreatic cancer is the fourth most common cause of death from cancer in the world and the sixth in Europe. Pancreatic cancer is more frequent in males than females. Worldwide, following diagnosis of pancreatic cancer, <2% of patients survive for 5 years, 8% survive for 2 years and <50% survive for only approx. 3 months. The biggest risk factor in pancreatic cancer is age, with a peak of morbidity at 65 years. Difficulty in the diagnosis of pancreatic cancer causes a delay in its detection. It is one of the most difficult cancers to diagnose and therefore to treat successfully. Additional detection of carbohydrate markers may offer a better diagnosis of pancreatic cancer. Carbohydrate markers of cancer may be produced by the cancer itself or by the body in response to cancer, whose presence in body fluids suggests the presence and growth of the cancer. The most widely used, and best-recognized, carbohydrate marker of pancreatic cancer is CA 19-9 [CA (carbohydrate antigen) 19-9]. However, the relatively non-specific nature of CA 19-9 limits its routine use in the early diagnosis of pancreatic cancer, but it may be useful in monitoring treatment of pancreatic cancer (e.g. the effectiveness of chemotherapy), as a complement to other diagnostic methods. Some other carbohydrate markers of pancreatic cancer may be considered, such as CEA (carcinoembryonic antigen), CA 50 and CA 242, and the mucins MUC1, MUC2 and MUC5AC, but enzymes involved in the processing of glycoconjugates could also be involved. Our preliminary research shows that the activity of lysosomal exoglycosidases, including HEX (N-acetyl-β-D-hexosaminidase), GAL (β-D-galactosidase), FUC (α-L-fucosidase) and MAN (α-D-mannosidase), in serum and urine may be used in the diagnosis of pancreatic cancer.     

Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens

The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19–9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19–9 in early-stage pancreatic cancer and the control groups. CA 19–9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70–74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19–9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9–9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19–9 data presented here will be useful for benchmarking and for exploring relationships to CA 19–9.     

血清miR-92a在胰腺癌诊断及预后评估中的临床意义研究

目的:探讨血清miR-92a在胰腺癌诊断和预后分析中的价值,为胰腺癌早诊断以及预后评估提供潜在的分子标志物。方法:回顾性分析我院及重庆医科大学附属第一、第二医院2014年8月~2016年12月收治的30例胰腺癌未转移患者、30例胰腺癌转移患者和30例慢性胰腺炎患者的临床资料,另选择同期在我院进行健康体检的30例健康人作为健康组。收集血清,应用定量PCR法检测各组血清miR-92a的表达水平,利用化学发光法检测各组血清中的糖蛋白抗原19-9(CA-19-9)含量。以ROC分析比较血清miR-92a与CA 19-9在胰腺癌诊断中的特异度、敏感性。结果:胰腺癌未转移组患者和胰腺癌转移组患者血清中miR-92a水平显著高于健康组和慢性胰腺炎组(P0.05),胰腺癌转移组患者血清中miR-92a水平显著高于胰腺癌未转移组患者(P0.05)。胰腺癌未转移组患者和胰腺癌转移组患者血清中CA19-9水平显著高于健康组和慢性胰腺炎组(P0.05)。miR-92a诊断胰腺癌的敏感度高于CA19-9和miR-92a+CA 19-9,而miR-92a+CA 19-9诊断胰腺癌的特异度显著高于miR-92a和CA19-9(P0.05),且有较高的胰腺癌转移预测应用价值。结论:血清miR-92a联合CA 19-9检测能够诊断胰腺癌,具有良好的敏感度和特异度,miR-92a还具有较好的胰腺癌转移预测价值,可作为胰腺癌早期无创筛查方法加以应用。     

Roles of CA19-9 in pancreatic cancer: Biomarker,predictor and promoter

Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.     

Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification

Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to investigate the clinical applicability of cyst fluid research obtained using surgical specimens. Matched pairs of operating-room collected (OR) and EUS-FNA samples from 12 patients were evaluated for the levels of three previously described biomarkers, CA 19-9, CEA, and glycan levels detected by wheat germ agglutinin on MUC5AC (MUC5AC-WGA). CA 19-9 and MUC5AC-WGA correlated well between the sample types, although CEA was more variable between the sample types for certain patients. The variability was not due to the time delay between EUS-FNA and OR collection or differences in total protein concentrations but may be caused by contamination of the cyst fluid with blood proteins. The classification of each patient based on thresholds for each marker was perfectly consistent between sample types for CA 19-9 and MUC5AC-WGA and mostly consistent for CEA. Therefore, results obtained using OR-collected pancreatic cyst fluid samples should reliably transfer to the clinical setting using EUS-FNA samples.     

Tumor markers in pancreatic cancer: a comparative clinical study between CEA, CA 19-9 and CA 50

Seventy-eight patients were evaluated to ascertain the usefulness of markers CA 19-9 and CA 50 in diagnosing pancreatic cancer, using a less specific marker (CEA) as reference. Three groups were considered: a) 36 controls; b) 22 patients with benign obstructive jaundice; c) 20 patients with pancreatic cancer. Preoperative blood samples were obtained to ascertain CEA (E.I.A.), CA 19-9 (R.I.A.) and CA 50 (T.R.-F.I.A.). Serum concentrations of the various markers were significantly higher for patients with pancreatic cancer in comparison with the other groups, at cut-offs of 10 ng/ml (CEA), 100 ng/ml (CA 19-9) and 170 U/ml (CA 50). The sensitivity of CA 19-9 (94%) and CA 50 (88%) was much greater than that of CEA (30%). The specificity of the three markers in patients with pancreatic cancer, with respect to the control group, was 100% and this figure is reduced with respect to the group suffering from benign obstructive jaundice (CEA: 90%; CA 19-9: 88% and CA 50: 87%). Diagnostic results (sensitivity, specificity, positive predictive value (P.P.V.) and negative predictive value (N.P.V.] did not significantly increase with respect to CA 19-9 and CA 50 when considered individually. It is concluded that the serum concentrations of CA 19-9 and CA 50 showed high sensitivity and specificity as markers of pancreatic cancer with respect to the other groups, pointing towards clinical routine clinical use of both markers. In addition, a comparative study of the literature has been made and prospects for short-term development and concrete applications for early and reliable diagnosis have been highlighted.     

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology

Background

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19–9 (CA 19–9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies.

Methods

CA 19–9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls.

Results

The combination of CA 19–9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19–9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients.

Conclusions

Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.     

CA19-9及CA72-4联合检测在胰腺癌诊断中的应用价值

目的:探究联合检测血清糖类抗原(CA)19-9和CA72-4水平在胰腺癌诊断中的应用价值。方法:回顾性选取我院2016年1月～2017年12月收治的72例胰腺癌患者作为胰腺癌组,以同期住院的68例良性胰腺病患者作为良性胰腺疾病组,同时纳入67例健康体检者作为对照组。检测三组人群血清CA19-9和CA72-4水平,采用受试者工作特征曲线(ROC曲线)及曲线下面积(AUC)分析评估各单项检测指标及联合检测指标对胰腺癌特异性诊断的价值。结果:胰腺癌组患者血清CA19-9和CA72-4水平分别为(137.69±25.32)U/mL和(6.96±1.25)U/mL,显著高于良性胰腺疾病组和对照组(P0.05)。血清CA19-9和CA72-4联合检测诊断胰腺癌的ROC曲线AUC高于其单独检测(P0.05),CA19-9和CA72-4的最佳临界值分别为86.94 U/m L和4.23 U/m L,此时联合检测诊断胰腺癌的敏感性为94.7%,特异性为95.2%。结论:联合检测血清CA19-9和CA72-4诊断胰腺癌的临床价值明显优于其单独检测。     

2010 Reviewers for Biotechnic & Histochemistry

Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (?) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (?), MUC2 (+) and CK17 (?), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (?) and CK17 (?) profile. More importantly, the MUC1 (+), MUC2 (?) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (?) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (?) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.     

Identification of a novel type of CA19-9 carrier in human bile and sera of cancer patients: an implication of the involvement in nonsecretory exocytosis

Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatic cancer. Although the CA19-9 level is measured using anti-sialyl Lewis A antibodies, it remains unknown which molecules carry CA19-9 other than mucins. Here we report the identification and characterization of a novel type of CA19-9 carrier, BGM (bile globular membrane), which is thought to exist in normal bile and to be secreted into sera of patients with pancreatic cancer. We purified the BGM from bile juice using a β-casein column because surface plasmon resonance analysis could detect such carrier vesicles binding to β-casein in sera of patients with pancreatic cancer. We identified characteristic molecules for BGM such as AHNAK (desmoykoin) and a novel golgin family member, CABIN (CAsein Binding domain integral protein with golgIN motif) by mass spectrometry analysis. BGM was detected in the sera of patients with pancreatic cancer as well as athymic mice with transplanted pancreatic cancer cells. Down regulation of CABIN inhibited the secretion of CA19-9 on BGM in pancreatic cancer cell lines. We measured and visualized BGM in sera of patients with cancer. Thus, BGM might be another CA19-9 carrier (glyco-lipids on membrane vesicles) other than mucins and could be applied to the diagnosis of pancreatic cancer.     

Human carcinoma-associated and salivary mucins detected by anti-bovine submaxillary mucin antibodies

Polyclonal rabbit anti-bovine submaxillary mucin antibodies, anti-BSM IgG, were analyzed by autoradiography and densitometry (after SDS electrophoresis and blotting), ELISA, and IRMA assays for reactivity against native antigen BSM, deglycosylated and desialylated BSM, and human salivary and carcinoma-associated mucins. Known human tumor marker CA19-9 antigen reacted with rabbit anti-BSM IgG under different conditions, either soluble or immobilized. As soluble antigen, in IRMA it reacted with anti-BSM antibodies used both as a catcher and a tracer, as well as in combination with monoclonal anti-CA19-9 antibodies as a catcher. MUC1 mucin is a carrier of this carbohydrate antigen, CA19-9, or sialyl-Lewis(a), as well as of CA15-3 antigen, a known breast tumor marker. Autoradiography and densitometry demonstrated binding of anti-BSM IgG to intact MUC1 in a sample of commercial standard preparation of CA19-9 antigen. The same method and analysis demonstrated binding of anti-BSM IgG to MUC1 and to smaller antigens of 85-120 kD in samples containing CA15-3 antigen: commercial standard preparation, human breast tissue, and human milk. In a sample of whole human saliva, reactions of both isoforms of MUC7 were detected by autoradiography, as bands of 85 and 115 kD, and densitogram analysis also demonstrated reaction with MUC5B. Chemical modifications performed as periodate oxidation and desialylation of the BSM demonstrated carbohydrate (i.e., sialic acid) epitope sensitivity for anti-BSM IgG. The results presented in this work indicate that polyclonal anti-BSM antibodies are specific for sialylated carbohydrate structure on mucins and could serve as a tool for investigation of human carcinoma-associated and salivary mucins.     

Human carcinoma-associated and salivary mucins detected by anti-bovine submaxillary mucin antibodies

Polyclonal rabbit anti-bovine submaxillary mucin antibodies, anti-BSM IgG, were analyzed by autoradiography and densitometry (after SDS electrophoresis and blotting), ELISA, and IRMA assays for reactivity against native antigen BSM, deglycosylated and desialylated BSM, and human salivary and carcinoma-associated mucins. Known human tumor marker CA19-9 antigen reacted with rabbit anti-BSM IgG under different conditions, either soluble or immobilized. As soluble antigen, in IRMA it reacted with anti-BSM antibodies used both as a catcher and a tracer, as well as in combination with monoclonal anti-CA19-9 antibodies as a catcher. MUC1 mucin is a carrier of this carbohydrate antigen, CA19-9, or sialyl-Lewis^a, as well as of CA15-3 antigen, a known breast tumor marker. Autoradiography and densitometry demonstrated binding of anti-BSM IgG to intact MUC1 in a sample of commercial standard preparation of CA19-9 antigen. The same method and analysis demonstrated binding of anti-BSM IgG to MUC1 and to smaller antigens of 85–120 kD in samples containing CA15-3 antigen: commercial standard preparation, human breast tissue, and human milk. In a sample of whole human saliva, reactions of both isoforms of MUC7 were detected by autoradiography, as bands of 85 and 115 kD, and densitogram analysis also demonstrated reaction with MUC5B. Chemical modifications performed as periodate oxidation and desialylation of the BSM demonstrated carbohydrate (i.e., sialic acid) epitope sensitivity for anti-BSM IgG. The results presented in this work indicate that polyclonal anti-BSM antibodies are specific for sialylated carbohydrate structure on mucins and could serve as a tool for investigation of human carcinoma-associated and salivary mucins.     

Granulocyte-macrophage-colony stimulating factor in patients with colorectal cancer

Granulocyte-macrophage-colony stimulating factor (GM-CSF) belongs to the group of glycoproteins called colony-stimulating factors (CSFs). It has been shown that the activity of CSFs is not limited to the hematopoietic cells but can also affect the proliferation of colon carcinoma cell lines. The purpose of this investigation was to compare the serum level of GM-CSF in colorectal cancer patients to a control group, to assess the level of GM-CSF in relation to the level of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), and to define the sensitivity, the specificity and the predictive values of GM-CSF in colorectal cancer. In this study, the serum level of tumour markers was measured in 30 patients with colorectal cancer and in 20 healthy subjects. GM-CSF was assayed using ELISA system, CEA and CA 19-9 were measured by MEIA. The serum levels of CEA, CA 19-9 and GM-CSF were higher in the patients with colorectal cancer than in the control group. The sensitivities of CEA (63%) and CA 19-9 (56%) were lower than the GM-CSF sensitivity (80%). The specificities of tumour markers were 70% (CEA, GM-CSF) and 75% for CA 19-9. The GM-CSF predictive v values were higher than the CEA and CA 19-9 values. These results suggest that GM-CSF may be useful as tumour marker in colorectal cancer, but further studies are needed.     

Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling

Pancreatic cancer is a lethal disease that is difficult to diagnose at early stages when curable treatments are effective. Biomarkers that can improve current pancreatic cancer detection would have great value in improving patient management and survival rate. A large scale quantitative proteomics study was performed to search for the plasma protein alterations associated with pancreatic cancer. The enormous complexity of the plasma proteome and the vast dynamic range of protein concentration therein present major challenges for quantitative global profiling of plasma. To address these challenges, multidimensional fractionation at both protein and peptide levels was applied to enhance the depth of proteomics analysis. Employing stringent criteria, more than 1300 proteins total were identified in plasma across 8-orders of magnitude in protein concentration. Differential proteins associated with pancreatic cancer were identified, and their relationship with the proteome of pancreatic tissue and pancreatic juice from our previous studies was discussed. A subgroup of differentially expressed proteins was selected for biomarker testing using an independent cohort of plasma and serum samples from well-diagnosed patients with pancreatic cancer, chronic pancreatitis, and nonpancreatic disease controls. Using ELISA methodology, the performance of each of these protein candidates was benchmarked against CA19-9, the current gold standard for a pancreatic cancer blood test. A composite marker of TIMP1 and ICAM1 demonstrate significantly better performance than CA19-9 in distinguishing pancreatic cancer from the nonpancreatic disease controls and chronic pancreatitis controls. In addition, protein AZGP1 was identified as a biomarker candidate for chronic pancreatitis. The discovery and technical challenges associated with plasma-based quantitative proteomics are discussed and may benefit the development of plasma proteomics technology in general. The protein candidates identified in this study provide a biomarker candidate pool for future investigations.     

CA 72-4 compared with CEA and CA 19-9 as a marker of some gastrointestinal malignancies

The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA 72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.     

CEA、CA19-9与CA72-4用于诊断老年胃癌的临床价值研究

目的:探讨CEA、CA19-9以及CA72-4诊断老年胃癌的临床价值。方法:对192例经活检确诊为老年胃癌患者的血清CEA、CA19-9以及CA72-4水平进行分析,比较不同TNM分期老年胃癌患者的血清CEA、CA19-9以及CA72-4阳性率,并评价血清CEA、CA19-9以及CA72-4水平诊断老年胃癌的敏感性和特异性。结果:TNM 3期及4期的胃癌患者CEA以及CA19-9阳性率明显高于1期及2期胃癌患者,而TNM1-4期的胃癌患者CA72-4的阳性率都明显高于CEA以及CA19-9。以6.5 ng/m L、30U/m L以及4 ng/m L分别作为CEA、CA19-9以及CA72-4的上限临界值,其诊断老年患者的胃癌的敏感性分别为15.6%、19.3%以及29.2%,特异性分别为98.9%、97.2%以及98.0%,曲线下面积分别为0.59、0.62以及0.66。结论:CEA、CA19-9以及CA72-4对于诊断老年胃癌都有较好的特异性,但敏感性一般,尤其对于早期胃癌,CEA及CA19-9敏感性较差,CA72-4敏感性要优于二者。