Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-asso...Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures.To overcome these obstacles,we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous,stromal,and healthy mucosa cells.N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatographyelectrospray ionization tandem mass spectrometry,enabling the differentiation and structural characterization of isomeric species.In total,116 N-glycans were identified that showed profound differences in expression among cancer,stroma,and normal mucosa.In comparison with healthy mucosa,the cancer cells showed an increase in a2-6 sialylation and monoantennary N-glycans,as well as a decrease in bisected N-glycans.Moreover,specific sialylated and(sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers.In comparison with cancer,the stroma showed lower levels of oligomannosidic and monoantennary N-glycans,LewisA/X epitopes,and sulfation,as well as increased expression of(core-)fucosylation and a2-3 sialylation.Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues,proving the necessity of their separate analysis for the discovery of cancer-associated glycans.展开更多
Ketodeoxynononic acid(Kdn)is a rather uncommon class of sialic acid in mammals.However,associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression.Hit...Ketodeoxynononic acid(Kdn)is a rather uncommon class of sialic acid in mammals.However,associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression.Hitherto,there has been a lack of conclusive evidence that Kdn occurs on(specific)human glycoproteins(conjugated Kdn).Here,we report for the first time that Kdn is expressed on prostate-specific antigen(PSA)N-linked glycans derived from human seminal plasma and urine.Interestingly,Kdn was found only in an a2,3-linkage configuration on an antennary galactose,indicating a highly specific biosynthesis.This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer(PCa),although no differences were found between PCa and nonPCa patients.Further research is needed to investigate the occurrence,biosynthesis,biological role,and biomarker potential of both free and conjugated Kdn in humans.展开更多
文摘Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures.To overcome these obstacles,we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous,stromal,and healthy mucosa cells.N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatographyelectrospray ionization tandem mass spectrometry,enabling the differentiation and structural characterization of isomeric species.In total,116 N-glycans were identified that showed profound differences in expression among cancer,stroma,and normal mucosa.In comparison with healthy mucosa,the cancer cells showed an increase in a2-6 sialylation and monoantennary N-glycans,as well as a decrease in bisected N-glycans.Moreover,specific sialylated and(sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers.In comparison with cancer,the stroma showed lower levels of oligomannosidic and monoantennary N-glycans,LewisA/X epitopes,and sulfation,as well as increased expression of(core-)fucosylation and a2-3 sialylation.Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues,proving the necessity of their separate analysis for the discovery of cancer-associated glycans.
基金supported by the Chinese Scholarship CouncilCure for Cancer FoundationAstellas Pharma B.V。
文摘Ketodeoxynononic acid(Kdn)is a rather uncommon class of sialic acid in mammals.However,associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression.Hitherto,there has been a lack of conclusive evidence that Kdn occurs on(specific)human glycoproteins(conjugated Kdn).Here,we report for the first time that Kdn is expressed on prostate-specific antigen(PSA)N-linked glycans derived from human seminal plasma and urine.Interestingly,Kdn was found only in an a2,3-linkage configuration on an antennary galactose,indicating a highly specific biosynthesis.This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer(PCa),although no differences were found between PCa and nonPCa patients.Further research is needed to investigate the occurrence,biosynthesis,biological role,and biomarker potential of both free and conjugated Kdn in humans.
