Dataset Information

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.

SUBMITTER: Ruhaak LR

PROVIDER: S-EPMC4644186 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.

Ruhaak L Renee LR Taylor Sandra L SL Stroble Carol C Nguyen Uyen Thao UT Parker Evan A EA Song Ting T Lebrilla Carlito B CB Rom William N WN Pass Harvey H Kim Kyoungmi K Kelly Karen K Miyamoto Suzanne S

Journal of proteome research 20150930 11

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 a ...[more]

PMID: 26322380

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Project description:Gene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes. Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation. 58 lung adenocarcinoma and 58 adjacent non-tumor lung fresh frozen tissues were macrodissected, and total RNA was isolated to be analyzed using the Illumina HumanWG-6 v3.0 expression beadchip.

Dataset Information

Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.

Publications

Differential N-Glycosylation Patterns in Lung Adenocarcinoma Tissue.

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