Dataset Information

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

ABSTRACT: BACKGROUND:Pancreatic cancer (PC) is a highly aggressive tumor with a poor prognosis that lacks specific diagnostic markers. Mucin 5AC (MUC5AC) is a member of the mucin family, a heterogeneous group of high molecular weight, heavily glycosylated proteins that could be either membrane-bound or secreted. This multi-central study is to evaluate the performance of serum MUC5AC in combination with carbohydrate antigen 19-9 (CA19-9) for the diagnosis of PC in Asian. METHODS:Sixty-one patients with PC (comprised of early pancreatic cancer [n = 30] and late pancreatic cancer [n = 31] patients), 29 benign control, 35 choledocholithiasis, 25 chronic pancreatitis, and 34 healthy controls, were recruited from two hospitals. Serum levels of MUC5AC were evaluated by commercial ELISA kits. CA19-9 was measured by chemiluminescence immunoassay. The cutoff value of MUC5AC was determined based on optimal sensitivity and specificity. RESULTS:Serum MUC5AC in patients with PC (210.1 [100.5-423.8] ng/mL) presented higher levels than those in controls. The combined biomarker panel (MUC5AC and CA19-9) presented better performance and improved specificity to differentiate PC from controls (AUC 0.894; 95% CI (0.844-0.943), sensitivity 0.738, specificity 0.886) than CA19-9 (p = 0.043) or MUC5AC alone (p = 0.010); however, the latter two had no difference (p = 0.824). CONCLUSIONS:Serum MUC5AC is a potential biomarker for PC. The combination with CA19-9 presents improved specificity and better performance.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7006398 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

Zhang Jiayu J Wang Yue Y Zhao Tiancheng T Li Yezhou Y Tian Leilei L Zhao Jinming J Zhang Jingxin J

World journal of surgical oncology 20200207 1

<h4>Background</h4>Pancreatic cancer (PC) is a highly aggressive tumor with a poor prognosis that lacks specific diagnostic markers. Mucin 5AC (MUC5AC) is a member of the mucin family, a heterogeneous group of high molecular weight, heavily glycosylated proteins that could be either membrane-bound or secreted. This multi-central study is to evaluate the performance of serum MUC5AC in combination with carbohydrate antigen 19-9 (CA19-9) for the diagnosis of PC in Asian.<h4>Methods</h4>Sixty-one pa ...[more]

PMID: 32028958

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Project description:OBJECTIVESPancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets.METHODSThe expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321).RESULTSTissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2?ng/ml, IQR: 23.9-382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7?ng/ml, IQR: 87.7-948.6) were significantly higher compared with (P-value ?0.0001) benign controls (BC) (7.2?ng/ml, IQR: 0.4-26.5) and (P-value ?0.0001) chronic pancreatitis (CP) controls (8.4?ng/ml, IQR: 1.5-19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls.CONCLUSIONSMUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Project description:CA19-9 values are regularly measured in patients with pancreatic cancer. Certainly, its potential as a biomarker has been compromised by false negative results in CA19-9 negative patients and false positive results in benign pancreatico-biliary diseases. For detection of PDAC recurrence, however, CA19-9 might play an important role. The aim of this study is to analyze the accuracy of CA19-9 for detecting recurrence of pancreatic cancer. All included patients were treated either at the University Medical Center Goettingen, or at the Department of Interdisciplinary Oncology and Pneumonology, DRK-Kliniken Nordhessen, Kassel. We analyzed data of 93 patients with pancreatic cancer in the training set and 41 in the validation set, both retrospectively. Pre- and postoperative CA19-9 values and results of imaging techniques were compared. We performed ROC-analysis. The association between longitudinally measured CA19-9 values and relapse was studied with a joint model between a random effects model for the longitudinal CA19-9 measurements and a Cox proportional hazards models for the survival data. In the test set (n = 93 patients) the median follow-up time was 644 days (22 months). Overall, 71 patients (76.3%) developed recurrence during follow-up. Patients with CA19-9 values of <10kU/l were considered as CA19-9 negative patients (n = 11) and excluded from further analysis. Among the rest, approximately 60% of the patients showed significantly elevated CA19-9 prior to detection of recurrence by imaging techniques. Recurrence was shown by 2.45 times elevated CA19-9 values with 90% positive predictive value. In the validation set, 2.45 times elevated CA19-9 values showed recurrence with 90% sensitivity and 83,33% specificity, with an area under the curve of 95%. Based on measured CA19-9 values during follow-up care, the joint model estimates in recurrence-free patients the probability of recurrence-free survival. CA19-9 elevation is an early and reliable sign for PDAC recurrence. On the strength of a very high accuracy in CA19-9 positive patients, it should be considered to use CA19-9 for therapy decision even without a correlate of imaging technics. Using the joint model, follow-up care of PDAC patients after curative therapy can be stratified.

Project description:Background: Although Carbohydrate antigen 19-9 (CA19-9) is considered clinically useful and informative for pancreatic carcinoma (PC), false positive results, and false negative results have restricted its clinical use. Especially missed or delayed diagnosis of PC patients with negative CA19-9 value limited the utility. To improve prognosis of PC patients, the discovery of reliable biomarkers to assist CA19-9 is desired. Serum IgG galactosylation based on our previous report was altered in PC patients comparing to healthy controls. The objective of this study was to explore the diagnostic significance of IgG galactosylation in assisting CA19-9 for PC in a comprehensive way. Methods: Serum IgG galactosylation profiles were analyzed by MALDI-MS in cohort 1 (n = 252) and cohort 2 in which all CA19-9 levels were negative (n = 133). In each cohort, not only healthy controls and PC patients but also benign pancreatic disease (BPD) patients were enrolled. Peaks were acquired by the software of MALDI-MS sample acquisition, followed by being processed and analyzed by the software of Progenesis MALDI. IgG Gal-ratio, which was calculated from the relative intensity of peaks G0, G1, and G2 according to the formula (G0/(G1+G2×2)), was employed as an index for indicating the distribution of IgG galactosylation. Results: The Gal-ratio was elevated in PC comparing with that in non-cancer group (healthy controls and BPD). The area under the receiver operating characteristic curve (AUC) of IgG Gal-ratio was higher than that of CA19-9 (0.912 vs. 0.814). The performance was further improved when Gal-ratio and CA19-9 were combined (AUC: 0.928). Meanwhile, Gal-ratio also had great diagnostic value with a sensitivity of 92.31% (AUC: 0.883) in detection of PC at early stage. Notably, IgG Gal-ratio has great sensitivity (90.63%) and specificity (76.81%) in CA19-9-negative PC patients. Conclusions: IgG Gal-ratio had a great performance in detection of PC and could be used to assist CA19-9 in improving diagnosis performance through early stage detection, differentiation from BPD, and PC diagnosis with CA19-9-negative level.

Project description:BackgroundMinimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome.Materials and methodsSecretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19-9 (CA19-9) were validated by enzyme-linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power.ResultsIn tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin-2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p < .001, AUC = 0.844). Combined expression of THBS2 and CA19-9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early- and late-stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19-9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin.ConclusionOur proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19-9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD.Implications for practiceThe combined plasma expression of thrombospondin-2 and carbohydrate antigen 19-9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.

Dataset Information

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

Publications

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

Similar Datasets

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