Dataset Information

Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients.

ABSTRACT: 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.

SUBMITTER: Zhong A

PROVIDER: S-EPMC6402387 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients.

Zhong Ailing A Qin Ruihuan R Qin Wenjun W Han Jing J Gu Yong Y Zhou Lei L Zhang Hongqin H Ren Shifang S Lu Renquan R Guo Lin L Gu Jianxin J

Frontiers in oncology 20190227

<b>Background:</b> 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 i ...[more]

PMID: 30873386

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Project description:Background and objectivePost-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts.MethodsA total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices.ResultsIn the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated.ConclusionOur research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Project description:Background: Obstructive jaundice is one of the most common symptoms which can be caused by both malignant and benign hepato-biliary-pancreatic diseases. The differences and the differential diagnostic roles of the serum CA19-9, total bilirubin (TBIL) and especially, the ratio of CA19-9 to TBIL in these patients have not been well elucidated. This study compared the differences and the differential diagnostic roles of the increase-folds of the serum CA19-9, TBIL and the ratio of increase-folds of CA19-9 to increase-folds of TBIL in 508 cases of malignant (MOJ) and benign (BOJ) obstructive jaundice patients. Methods: Totally, 508 cases of obstructive jaundice patients with pathological results were retrospectively enrolled. 342 cases were MOJ, including gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, periampullar adenocarcinoma and pancreatic adenocarcinoma.The other 166 cases were BOJ, including cholelithiasis, primary sclerosing cholangitis (PSC), IgG4 related sclerosing cholangitis (IRSD), inflammatory stricture of bile duct, and adenoma. The data of the increase-folds of serum CA19-9, TBIL and the ratio of increase-folds of CA19-9 to increase-folds of TBIL was collected and analyzed. The ROC (receiver operating characteristic) curve was adopted to determine the optimal cutoff value to evaluate their differential diagnostic roles. Results: The CA19-9 was elevated in 94.15% of the MOJ, compared to 67.10% in BOJ (P<0.0001). The increase-folds of the CA19-9 (76.52±15.04 vs 3.55±0.41, P< 0.0001) and the increase-folds of TBIL (7.10±0.25 vs 5.95±0.36, P=0.0034) and the ratio (14.96±5.05 vs 0.79±0.93, P=0.0026) in MOJ were significantly higher than BOJ. The ROC curves indicated that the TBIL showed minimal differential diagnostic power (AUC=0.590), the increase-folds of CA19-9 and the ratio showed stronger differential diagnostic power (AUC=0.815 and AUC=0.889, respectively). The optimal value of the increase-folds of serum CA19-9 and the ratio for differential diagnosis was 4.5 and 0.88, respectively. Further, the combination of the increase-folds of serum CA19-9 and the ratio could increase the specificity and accuracy of the diagnosis of MOJ. Conclusion: The serum CA19-9, TBIL and the ratio in MOJ and BOJ are significantly different. The ratio of the increase-folds of CA19-9 to increase-folds of TBIL has stronger differential diagnostic roles than the increase-folds of CA19-9 or TBIL alone. The combination of the increase-folds of the CA19-9 and the ratio can further improve the specificity and accuracy of the diagnosis of MOJ.

Dataset Information

Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients.

Publications

Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients.

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