Abstract:BACKGROUND:The objectives of this study were to identify and validate the diagnostic value of N-glycan markers in colorectal cancer (CRC) and to uncover their underlying molecular mechanism. METHODS: In total, 347 individuals, including patients with CRC, patients with colorectal adenoma, and healthy controls, were divided randomly into a training group (n ¼ 287) and retrospective validation groups (n ¼ 60). Serum N-glycan profiling was analyzed by DNA sequencer-assisted/flurophore-assisted carbohydrate electr… Show more
“…DSA-FACE is a simple and efficient technology for measuring N-glycan changes in serum. We previously used the technology to assist in the diagnosis of HCC, CRC, and gastric cancer [29][30][31]. The study was designed to target analysis of the aberrant N-glycans.…”
Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.
“…DSA-FACE is a simple and efficient technology for measuring N-glycan changes in serum. We previously used the technology to assist in the diagnosis of HCC, CRC, and gastric cancer [29][30][31]. The study was designed to target analysis of the aberrant N-glycans.…”
Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.
“…Moreover, increased sialylation (mainly derived from α-2,3-linked sialic acid) of serum proteins was confirmed by MAL II-binding lectin blot analysis in LCMM patients. The decreased core-fucosylation has also been reported in colorectal cancer, gastric cancer and breast carcinoma, and an increase in sialylation was also found in breast cancer [19, 32–33]. Recently, Glavey SV et al reported that high expression of ST3GAL6, an α-2,3-linked sialyltransferase, could influence homing and survival in multiple myeloma [34].…”
Section: Discussionmentioning
confidence: 99%
“…DSA-FACE, which we applied in this study, provides a convenient, non-invasive, excellent sensitive method to detect desialylated N-glycan profiling in serum and may be more practical for routine clinical analysis. This technique was previously used to assist in the diagnosis of various cancers, such as Hepatocellular Carcinoma (HCC), colorectal cancer and gastric cancer [19,20,27]. As we have mentioned before, SPE and IFE are poor at detecting free light chains.…”
The aim of this study was to evaluate the diagnostic and differential diagnostic power of serum N-glycans for light chain multiple myeloma (LCMM). A total of 167 cases of subjects, including 42 LCMM, 42 IgG myeloma, 41 IgA myeloma, and 42 healthy controls were recruited in this study. DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) was applied to determine the quantitive abundance of serum N-glycans. The core fucosylated, bisecting and sialylated modifications were analyzed in serum of LCMM patients (n=20) and healthy controls (n=20) randomly selected from the same cohort by lectin blot. Moreover, serum sialic acid (SA) level was measured by enzymatic method. We found two N-glycan structures (NG1A2F, Peak3; NA2FB, Peak7) showed the optimum diagnostic efficacy with area under the ROC curve (AUC) 0.939 and 0.940 between LCMM and healthy control. The sensitivity and specificity of Peak3 were 88.1% and 92.9%, while Peak7 were 92.9% and 97.6%, respectively. The abundance of Peak3 could differentiate LCMM from IgG myeloma with AUC 0.899, sensitivity 100% and specificity 76.2%, and Peak7 could be used to differentiate LCMM from IgA myeloma with AUC 0.922, sensitivity 92.9% and specificity 82.9%. Serum SA level was significantly higher in patients with LCMM than that in healthy controls. Moreover, the decreased core fucosylation, bisecting and increased sialylation characters of serum glycoproteins were observed in patients with LCMM. We concluded that serum N-glycan could provide a simple, reliable and non-invasive biomarker for LCMM diagnosis and abnormal glycosylation might imply a new potential therapeutic target in LCMM.
“…Serum glycomic studies to discover novel glycan cancer biomarkers have been highlighted (Adamczyk et al 2012 ). Numerous glycan tumor marker candidates for various cancers, including liver (Kaji et al 2013 ;Kamiyama et al 2013 ;Wu et al 2012 ;Tang et al 2010 ;Goldman et al 2009 ;Comunale et al 2009 ;Tanabe et al 2008 ;Ressom et al 2008 ), ovary (Biskup et al 2013 ;Hua et al 2013 ;Alley et al 2012 ;Abbott et al 2010 ;Leiserowitz et al 2008 ), pancreas (Li et al 2009 ;Okuyama et al 2006), breast (de Leoz et al 2011Alley et al 2010 ;Zeng et al 2010 ;Storr et al 2008 ;Abd Hamid et al 2008 ;Kyselova et al 2008 ;Kirmiz et al 2007 ), prostate , lung (Arnold et al 2011 ), colorectum (Zhao et al 2012 ), bile duct (Silsirivanit et al 2011 ), and esophagus ) cancers, have been reported. Most of these glycomic analyses have been carried out by newly developed high-throughput platform technologies, such as mass spectrometry-based methods and lectin-based methods, which have enabled the effi cient analysis of large cohorts of samples.…”
Section: Glycomic Studies On Serum Of Cancer Patientsmentioning
Remarkable alterations in oligosaccharide structures are associated with many human diseases, including cancers. Numerous clinicopathological and biochemical studies have suggested the involvement of aberrant glycosylation in cancer malignancy, such as metastasis and invasion. Furthermore, altered carbohydrate determinants, including tumor-associated carbohydrate antigens such as SLe a (CA19-9), have been utilized as useful tumor markers for the diagnosis of cancer. Cancer glycomic analysis (i.e., precise and comprehensive analysis of altered oligosaccharides in cancer tissues and sera) is a widely used tool for (1) investigating the involvement of glycosylation in cancer malignancy and (2) discovering novel carbohydrate tumor marker candidates. Comprehensive clinico-glycomic studies of glycosphingolipids of colorectal cancers have revealed specifi c alterations related to malignant transformation, as well as characteristic alterations associated with clinical features. Glycomic analyses of colorectal cancers and pancreatic cancers revealed the presence of two kinds of novel fucogangliosides, sialylated type1H (Lewis-negative specifi c antigen) and sialylated type2H, both of which are isomers of sialyl Le x and sialyl Le a . The accumulation of free oligosaccharides in human cancers has been elucidated. Free Neu5Ac-containing complex-type N -glycans accumulated in pancreatic cancers. In addition to these free oligosaccharides, free KDN-containing complex-type N -glycans accumulated in prostate cancers. N -linked and O -linked glycans have also been targets for cancer glycomics. In particular, extensive studies of serum glycomic analyses have been performed to fi nd novel glycan cancer biomarker utilizing newly developed high-throughput platform technologies. It is anticipated that these cancer glycomic studies will lead to the discovery of glycan biomarker or therapy targets for cancers.
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