ABSTRACT
Lung cancer has one of the highest mortality rates of malignant neoplasms. Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer. DNA methylation is more stable than gene expression and could be used as a biomarker for early tumor diagnosis. This study is aimed to screen potential DNA methylation signatures to facilitate the diagnosis and prognosis of LUAD and integrate gene expression and DNA methylation data of LUAD to identify functional epigenetic modules. We systematically integrated gene expression and DNA methylation data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), bioinformatic models and algorithms were implemented to identify signatures and functional modules for LUAD. Three promising diagnostic and five potential prognostic signatures for LUAD were screened by rigorous filtration, and our tumor-normal classifier and prognostic model were validated in two separate data sets. Additionally, we identified functional epigenetic modules in the TCGA LUAD dataset and GEO independent validation data set. Interestingly, the MUC1 module was identified in both datasets. The potential biomarkers for the diagnosis and prognosis of LUAD are expected to be further verified in clinical practice to aid in the diagnosis and treatment of LUAD.
ABSTRACT
Sulfated fucans from sea urchin egg jelly express well-defined chemical structures that vary with species. This species specificity regulates the sperm acrosome reaction, a critical step to assure intra-specific fertilization. In addition, these polysaccharides are involved in other biological activities such as anticoagulation. Although sulfation patterns are relevant to the levels of response in both activities, conformation and dynamics of these glycans are also contributing factors. However, data about these features of sulfated fucans are very rare. To address this, we have employed nuclear magnetic resonance experiments combined with molecular dynamics on structurally defined oligosaccharides derived from two sulfated fucans. The results have indicated that the oligosaccharides are flexible in solution. Ring conformation of their composing units displays just the (1)C4 chair configuration. In a particular octasaccharide, composed of two tetrasaccharide sequences, inter-residual hydrogen bonds play a role to decrease dynamics in these repeating units. Conversely, the linking disaccharide [-3)-α-L-Fucp-2(OSO3(-))-(1-3)-α-L-Fucp-4(OCO3(-))-(1-] located right between the two tetrasaccharide units has amplified motions suggested to be promoted by electrostatic repulsion of sulfates on opposite sides of the central glycosidic bond. This conjunction of information about conformation and dynamics of sulfated fucan oligosaccharides provides new insights to explain how these glycans behave free in solution and influenced by sulfation patterns. It may also serve for future studies concerning structure-function relationship of sulfated fucans, especially those involving sea urchin fertilization and anticoagulation.