Secretome-based identification of ULBP2 as a novel serum marker for pancreatic cancer detection

Background

To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues.

Methods

ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9).

Results

Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls.

Conclusions

Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening.     

Serum CA19–9, cathepsin D,and matrix metalloproteinase‐7 as a diagnostic panel for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of pancreatic cancers. CA19‐9 is not widely used for screening PDAC due to its low sensitivity. Here, we studied the clinical usefulness of cathepsin D, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) for screening patients with PDAC. A total of 248 patients with PDAC and 216 control subjects were recruited (109 PDAC patients and 70 controls in the training set and 139 PDAC patients and 146 controls in the validation set). We measured serum levels of cathepsin D, TIMPs (?1, ?3, and ?4), and MMPs (?1, ?7, ?8, and ?9) using Fluorokine MAP multiplex kits. The concentrations of cathepsin D and MMP‐7 were significantly higher in PDAC subjects than control subjects. In the training set, the diagnostic sensitivity and AUC of the panel of CA19‐9, cathepsin D, and MMP‐7 for PDAC were increased to 88% and 0.900, compared to 74% and 0.835 of CA19‐9 single marker at 80% specificity. The sensitivity using cut‐off value of biomarker panel was significantly increased in the validation set as well as training set. Our findings indicate that a serum biomarker panel consisting of CA19‐9, cathepsin D, and MMP‐7 may provide the most effective screening test currently feasible for PDAC.     

Development of candidate biomarkers for pancreatic ductal adenocarcinoma using multiple reaction monitoring

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of cancer mortality in the United States. Because CA 19-9 increases not only in PDAC, but also in benign conditions, there is urgent need for an additional PDAC biomarker. Isotope tags for relative and absolute quantification (iTRAQ) were performed using 6 pairs of PDAC and normal tissues from the same patients, to obtain preliminary PDAC-specific proteins; and verification was performed by multiple reactions monitoring (MRM), using 30 PDAC and 20 normal serum, targeting high-abundant serum proteins without any pre-preparation. As a result, 17 candidate proteins from tissue iTRAQ were verified as potential markers (AUC values > 0.7). Multivariate analysis (MA) demonstrated that a 6-marker panel, consisting of alpha-1 antitrypsin, haptoglobin beta chain, hemopexin, transferrin, zinc alpha-2 glycoprotein, and apolipoprotein A4 from the MRM result, had comparable discriminatory power versus CA 19-9. Our study demonstrated that a combination of iTRAQ on PDAC tissue and verification MRM-MA on individual serum was an efficient method for the development of PDAC multimarkers.     

Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.     

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。     

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.     

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.     

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients

The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary.     

TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis

The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.     

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.     

Value of CA 19-9 assay in serum and duodenal juice in the differential diagnosis of pancreatic disease

Levels of CA 19-9 in the serum and duodenal juice of nine patients with pancreatic adenocarcinoma (PC), ten patients with chronic calcifying pancreatitis (CCP) and ten healthy volunteers (C) were determined by immunoassay. Duodenal juice was obtained by duodenal intubation during the secretin caerulein test. Elevated CA 19-9 levels in the serum were significantly more frequent in PC than in CCP patients, but two PC patients gave levels only slightly above the cut-off value of 37 U/ml. CA 19-9 levels in duodenal juice were significantly higher in PC than in CCP patient, but there was some overlap between them; no overlapping was seen between PC or CCP group and controls. Two PC patients with duodenal juice CA 19-9 levels overlapping those of CCP were the same who showed only a slight rise in serum CA 19-9 levels. The CA 19-9 to total protein ratio in duodenal juice did not permit better discrimination between PC and CCP. We conclude that CA 19-9 assay in duodenal juice can differentiate healthy subjects from patients with pancreatic diseases, but it cannot improve the differential diagnosis between CCP and PC patients with a slight rise of CA 19-9 levels in serum.     

Angiopoietin-2 and Biliary Diseases: Elevated Serum,but Not Bile Levels Are Associated with Cholangiocarcinoma

Background

The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.

Aim

To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.

Methods

Bile and serum Angpt-2 levels were measured in patients with CC (n = 45), PSC (n = 74), CC complicating PSC (CC/PSC) (n = 11) and patients with bile duct stones (n = 37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.

Results

Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74–0.93 versus 0.65–0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.

Conclusions

Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.     

Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study

BackgroundThe clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.MethodsSixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).ResultsThe panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.ConclusionsMost biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.     

硫氧还蛋白还原酶：一种新型有效的胃癌化疗疗效监测标志物

胃癌是国际上发病率较高的肿瘤,寻找新型有效的肿瘤标志物用于胃癌的诊断和疗效评估,对于胃癌的临床治疗有较大的帮助。本研究选取经临床确诊的155例胃癌患者为研究对象,探究血浆硫氧还蛋白还原酶（thioredoxin reductase, TR）在胃癌化疗后临床获益人群与未获益人群中检测水平的差异,以及其与治疗效果的关系。结果显示,未获益组TR阳性率为82.67%,显著高于获益组TR阳性率（48.94%）。受试者操作特征曲线（receiver operating characteristic curve,ROC）分析显示,未获益组人群与获益组人群的TR活性诊断阈值为8.95 U/mL,ROC曲线下面积（area under the curve,AUC）为0.8423,明显优于常规胃癌标志物癌胚抗原（carcinoembryonic antigen,CEA）,肿瘤特异性抗原（cancer antigen,CA）19-9和CA72-4。同时,TR与常规胃癌标志物的联合检测提高阳性检出率至98.49%。TR被认为是一种新型的胃癌临床化疗疗效监测标志物,与临床疗效评价具有较高的一致性。     

硫氧还蛋白还原酶：一种新型有效的胃癌化疗疗效监测标志物

胃癌是国际上发病率较高的肿瘤,寻找新型有效的肿瘤标志物用于胃癌的诊断和疗效评估,对于胃癌的临床治疗有较大的帮助。本研究选取经临床确诊的155例胃癌患者为研究对象,探究血浆硫氧还蛋白还原酶（thioredoxin reductase, TR）在胃癌化疗后临床获益人群与未获益人群中检测水平的差异,以及其与治疗效果的关系。结果显示,未获益组TR阳性率为82.67%,显著高于获益组TR阳性率（48.94%）。受试者操作特征曲线（receiver operating characteristic curve,ROC）分析显示,未获益组人群与获益组人群的TR活性诊断阈值为8.95 U/mL,ROC曲线下面积（area under the curve,AUC）为0.8423,明显优于常规胃癌标志物癌胚抗原（carcinoembryonic antigen,CEA）,肿瘤特异性抗原（cancer antigen,CA）19-9和CA72-4。同时,TR与常规胃癌标志物的联合检测提高阳性检出率至98.49%。TR被认为是一种新型的胃癌临床化疗疗效监测标志物,与临床疗效评价具有较高的一致性。     

Validation of LRG1 as a Potential Biomarker for Detection of Epithelial Ovarian Cancer by a Blinded Study

Background

Leucine-rich alpha-2-glycoprotein (LRG1) was found to be differentially expressed in sera from patients with Epithelial Ovarian Cancer (EOC). The aim of this study is to investigate the performance of LRG1 for detection of EOC, including early stage EOC, and to evaluate if LRG1 can complement CA125 in order to improve EOC detection using two independent blinded sample sets.

Methods and Results

Serum LRG1 and CA125 were measured by immunoassays. All assays were performed blinded to clinical data. Using the two independent sample sets (156 participants for sample set 1, and 233 for sample set 2), LRG1 was differentially expressed in EOC cases as compared to healthy, surgical, and benign controls, and its performance was not affected by the conditions of blood collection. The areas under the ROC curve (AUC) for LRG1 in differentiating EOC cases from non-cases were 0.797 and 0.786 for sample set 1 and 2. For differentiating EOC cases from healthy controls, the AUC values for LRG1 were 0.792 and 0.794. At a fixed specificity of 95%, LRG1 detects 52%, and 53.5% of EOC cases from healthy controls for sample set 1 and 2. When combining LRG1 and CA125, the AUC value increased to 0.927, which was improved compared to CA125 (AUC=0.916) (p=0.008) alone in distinguishing EOC cases from non-cases. More importantly, LRG1 also showed potential performance in differentiating early stage EOC from non-cases with an AUC of 0.715 for sample set 1, and 0.690 for sample set 2. The combination of LRG1 and CA125 resulted in an AUC of 0.838, which outperforms CA125 (AUC=0.785) (p=0.018) in detecting early stage EOC cases from non-cases using the larger sample set.

Conclusions

LRG1 could be a useful biomarker alone or in combination with CA125 for the diagnosis of ovarian cancer.     

化学发光蛋白芯片用于检测肝癌患者血清CA19-9水平的方法研究

目的:探讨一种简单、有效、低成本、低耗时的化学发光蛋白芯片方法用于检测血清中的糖链抗原19-9(Carbohydrate Antigen19-9,CA19-9),以有助于对原发性肝癌的早期辅助诊断。方法:预先在醛基芯片上包被鼠源CA19-9单克隆抗体,建立CA19-9抗体蛋白芯片,共筛选出46份肝癌血清和32份正常健康人血清,然后用蛋白芯片方法进行检测,并以化学发光成像对检测结果进行判定。结果:24份肝癌血清的CA19-9水平高于37 U/m L,22份肝癌血清的CA19-9水平低于37 U/m L;30份正常人血清CA19-9含量低于37 U/m L,2份正常人血清的CA19-9含量为37 U/m L;灵敏度为52.17%,特异性为93.75%,ROC曲线下面积0.688[95%CI:0.566,0.811]。结论:本研究成功的建立了血清CA19-9的化学发光蛋白芯片检测方法。     

Identification and Confirmation of Differentially Expressed Fucosylated Glycoproteins in the Serum of Ovarian Cancer Patients Using a Lectin Array and LC-MS/MS

In order to discover potential glycoprotein biomarkers in ovarian cancer, we applied a lectin array and Exactag labeling based quantitative glycoproteomics approach. A lectin array strategy was used to detect overall lectin-specific glycosylation changes in serum proteins from patients with ovarian cancer and those with benign conditions. Lectins, which showed significant differential response for fucosylation, were used to extract glycoproteins that had been labeled using isobaric chemical tags. The glycoproteins were then identified and quantified by LC-MS/MS, and five glycoproteins were found to be differentially expressed in the serum of ovarian cancer patients compared to benign diseases. The differentially expressed glycoproteins were further confirmed by lectin-ELISA and ELISA assay. Corticosteroid-binding globulin (CBG), serum amyloid p component (SAP), complement factor B (CFAB), and histidine-rich glycoprotein (HRG) were identified as potential markers for differentiating ovarian cancer from benign diseases or healthy controls. A combination of CBG and HRG (AUC = 0.825) showed comparable performance to CA125 (AUC = 0.829) in differentiating early stage ovarian cancer from healthy controls. The combination of CBG, SAP, and CA125 showed improved performance for distinguishing stage III ovarian cancer from benign diseases compared to CA125 alone. The ability of CBG, SAP, HRG, and CFAB to differentiate the serum of ovarian cancer patients from that of controls was tested using an independent set of samples. Our findings suggest that glycoprotein modifications may be a means to identify novel diagnostic markers for detection of ovarian cancer.     

Thioredoxin Reductase: a New and Effective Biomarker for Monitoring the Efficacy of Chemotherapy in Gastric Cancer北大核心CSCD

Gastric cancer (GC) is one of the leading malignancies around the world. Identification of novel and efficient biomarkers for evaluation of therapeutic efficiency in GC could improve the therapeutic strategy in future clinical application. In the current study, a total of 155 GC patients were enrolled to evaluate the levels of plasma thioredoxin reductase (TR) activity to confirm its validity and efficacy in the evaluation of GC therapeutic efficiency. In GC patients after chemotherapy, plasma TR activity was remarkably higher in patients with progressive disease or uncontrolled condition (sensitivity 82. 67%) as compared with patients with complete or partial response (sensitivity 48. 94%) after chemotherapy (P < 0. 001). TR activity displayed the higher efficiency to distinguish between GC patients with two distinct clinical outcomes than carcinoembryonic antigen (CEA), cancer antigen 72-4 (CA72-4) and cancer antigen 19-9 (CA19-9), with a cut-off value of 8. 95 U / mL and AUC of 0. 8423 based on receiver operating characteristic (ROC) analysis. Moreover, combination of TR with other tumor markers (sensitivity 98. 49%) was demonstrated to be more effective in the evaluation of GC therapeutic efficiency than individual biomarker. Together, plasma TR activity was identified as a novel and efficient biomarker for the evaluation of therapeutic efficiency in GC. © 2019 The Author(s).     

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。