title: Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.
abstract: To decrease the mortality of lung cancer, better screening and diagnostic tools as well as treatment options are needed. Protein glycosylation is one of the major post-translational modifications that is altered in cancer, but it is not exactly clear which glycan structures are affected. A better understanding of the glycan structures that are differentially regulated in lung tumor tissue is highly desirable and will allow us to gain greater insight into the underlying biological mechanisms of aberrant glycosylation in lung cancer. Here, we assess differential glycosylation patterns of lung tumor tissue and nonmalignant tissue at the level of individual glycan structures using nLC-chip-TOF-MS. Using tissue samples from 42 lung adenocarcinoma patients, 29 differentially expressed (FDR < 0.05) glycan structures were identified. The levels of several oligomannose type glycans were upregulated in tumor tissue. Furthermore, levels of fully galactosylated glycans, some of which were of the hybrid type and mostly without fucose, were decreased in cancerous tissue, whereas levels of non- or low-galactosylated glycans mostly with fucose were increased. To further assess the regulation of the altered glycosylation, the glycomics data was compared to publicly available gene expression data from lung adenocarcinoma tissue compared to nonmalignant lung tissue. The results are consistent with the possibility that the observed N-glycan changes have their origin in differentially expressed glycosyltransferases. These results will be used as a starting point for the further development of clinical glycan applications in the fields of imaging, drug targeting, and biomarkers for lung cancer.
authors: L Renee
authors: LR
authors: Ruhaak
authors: Sandra L
authors: SL
authors: Taylor
authors: Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center , Sacramento, California 95817, United States.
authors: Carol
authors: C
authors: Stroble
authors: Uyen Thao
authors: UT
authors: Nguyen
authors: Evan A
authors: EA
authors: Parker
authors: Ting
authors: T
authors: Song
authors: Carlito B
authors: CB
authors: Lebrilla
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine , New York, New York 10016, United States.
authors: William N
authors: WN
authors: Rom
authors: Department of Cardiothoracic Surgery, NYU Langone Medical Center , New York, New York 10016, United States.
authors: Harvey
authors: H
authors: Pass
authors: Kyoungmi
authors: K
authors: Kim
authors: Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center , Sacramento, California 95817, United States.
authors: Karen
authors: K
authors: Kelly
authors: Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center , Sacramento, California 95817, United States.
authors: Suzanne
authors: S
authors: Miyamoto
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D002240:Carbohydrate Sequence; D005260:Female; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D005690:Galactose / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D054794:Glycomics / Q000379:methods; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D009363:Neoplasm Proteins; D011134:Polysaccharides; D005643:Fucose; D016695:Glycosyltransferases; D008358:Mannose; D005690:Galactose
keywords: N-Glycosylation; NSCLC; gene expression; nLC−MS profiling; tissue