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Purpose Dental pellicle formation starts instantaneously after oral hygiene due to the adsorption of salivary proteins to all orally exposed surfaces. The pellicle acts as a physiological mediator, protects the tooth surface from mechanical damages and reduces acid-induced enamel demineralization. The aim of this pilot study is to identify and characterize individual proteomic profiles of the initial pellicle formed on dental enamel and to compare the profiles with the corresponding saliva to analyze specific adsorption patterns occurring during pellicle formation. Experimental design The 3-min pellicle of five subjects formed in situ on bovine enamel is eluted chemically and analyzed separately by nano-mass spectrometry. The analysis of the corresponding saliva is conducted in parallel. Results Up to 498 pellicle proteins and up to 1032 salivary proteins are identified on an individual level. Comparison of the salivary and pellicle protein profiles demonstrates the pellicle formation to be highly individual. Nineteen proteins are significantly enriched in the 3-min pellicle of all subjects and 22 proteins are significantly depleted indicating that pellicle formation relies on selective adsorption. Conclusions and clinical relevance The short-term enamel pellicle is composed of several hundreds of adsorbed salivary proteins and reveals a highly individual proteomic profile.

The insulin-like growth factor 2 (IGF2) mRNA binding protein IMP2 (IGF2BP2) is an oncogenic protein known to be overexpressed in different tumor types. Pancreatic cancer is a very lethal cancer that requires early diagnosis and new treatment options. The aim of our study was to investigate the role of IMP2 in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). IMP2 was significantly overexpressed in a human precursor (PanIN) lesions suggesting IMP2 as a marker for early stages of PDAC. In a PDAC cohort of matched normal and tumor samples IMP2 showed overexpression in tumor tissues compared with normal pancreatic tissue. Strict correlation analysis (threshold R2 &gt, 0.75) revealed 22 genes highly positively and 9 genes highly negatively correlating with IMP2. Besides genes involved in the inhibition of apoptosis (Bcl-XL), especially factors involved in ubiquitination were strongly correlated with IMP2 expression: SMURF1 and FBXO45. Moreover, protein kinase C (PKC) signaling pathway was distinctly affected: DXS1179E encoding PKC iota, PKC substrate PLEK2, and inositol triphosphate receptor IP3R3 were positively correlated with IMP2 expression. Besides tumor initiation, IMP2 also seemed to have an impact on tumor progression. TGF-&beta, treatment of Panc-1 pancreatic cancer cells to induce epithelial-mesenchymal transition (EMT) was accompanied by increased IMP2 expression. EMT is important for cancer cells to gain migratory and invasive potential, which is essential for metastasis. Concordantly, circulating tumor cells showed higher IMP2 levels as compared with normal tissue from tumor origin and with normal hematological cells. Accordingly, IMP2 protein levels correlated with poor survival. In conclusion, as IMP2 seems to promote tumor progression of PDAC, it might be an interesting diagnostic and prognostic marker as well as a novel target for the treatment of PDAC.

Purpose To 1) elucidate individual proteomic profiles of the 3-min biofilm of caries-active and caries-free individuals and 2) compare these proteomic profiles against the background of caries. Experimental design The initial oral pellicle of 12 caries-active and 12 caries-free individuals is generated in situ on ceramics specimens. The individual, host-specific proteomic profiles of this basic pellicle layer are analyzed by a chemical elution protocol combined with an elaborate mass spectrometry and evaluated bioinformatically. Results A total of 1188 different proteins are identified. Additionally, 68 proteins are present in the profiles of all individuals, suggesting them as ubiquitously occurring base-proteins of the initial human pellicle. Thereof, the single profiles exhibit high inter-individual differences independent of their group affiliation, stating the initial pellicle to represent a rather "individual fingerprint". Quantitative analyses imply slight indication for 23 proteins potentially capable of counting for caries-specific biomarkers. Conclusions and clinical relevance The introduced protocol enables the individual analysis of minimal protein amounts and allows for highly precise characterizations and comparisons of individual proteomic profiles. The results contain a considerable higher extent of protein identifications and might serve as a base for future large scale analyzes to identify discrimination factors for the development of caries susceptibility tests.

Expression and methylation datasets are standard genomic techniques and an increasing number of computational methods are implemented to aid in analyzing the huge and complex amount of generated data. Such generated datasets often contain a sizeable fraction of outliers that cause misleading results in downstream analysis. Here, we present a comprehensive approach to detect sample and gene outliers in expression or methylation datasets. The core algorithms detected most outliers that were artificially introduced by us. Sample outliers detected by hierarchical clustering are validated by the Silhouette coefficient. At the gene level, the GESD, Boxplot, and MAD algorithms detected with f-measure of at least 83% the simulated outlier genes in non-intersected distributions. This combined approach detected many outliers in publicly available datasets from the TCGA and GEO portals. Frequently, some functionally similar genes marked as outliers turned out to have outlier observations in common samples. As such cases may be of special interest, they are labeled for further investigations. Expression and DNA methylation datasets should clearly be checked for outlier points before proceeding with any further analysis. We suggest that already 2 outlier observations are enough to label an outlier gene as they are enough to ruin a perfect co-expression. Besides, outliers might also carry useful information and thus functionally similar outliers should be labeled for further investigation. The presented software is freely available via github

// Ahmad Barghash 1, 2 , Nicole Golob-Schwarzl 3 , Volkhard Helms 1 , Johannes Haybaeck 3 , Sonja M. Kessler 4 1 Center for Bioinformatics, Saarland University, Saarbruecken, Germany 2 School of Computer Engineering and Information Technology, German Jordanian University, Amman, Jordan 3 Institute of Pathology, Medical University of Graz, Austria 4 Department of Pharmacy, Pharmaceutical Biology, Saarland University, Saarbruecken, Germany Correspondence to: Sonja M. Kessler, email: s.kessler@mx.uni-saarland.de Keywords: IGF2BP2/IMP2/p62, barret’s esophagus, esophageal squamous carcinoma, esophageal adenocarcinoma, metastasis Received: November 17, 2015 Accepted: June 26, 2016 Published: July 06, 2016 ABSTRACT Esophageal adenocarcinoma (EAC) represents the sixth leading cause of cancer-related deaths and develops in Barret’s esophagus affected tissues. The IGF2 mRNA binding protein IMP2/IGF2BP2/p62 was originally identified as an autoantigen in hepatocellular carcinoma. Aim of this study was to investigate the expression and prognostic role of IMP2 in EAC. Human EAC and Barret’s esophagus tissue showed overexpression of IMP2, particularly in tumors of increased size and in metastatic tissues. Molecular classification based on published gene signatures of esophageal cancer revealed a specific subtype, in which the expression of IMP2 is high. According to GO and KEGG pathway analyses, genes showing highly correlated expression with IMP2 are associated with growth, proliferation, metabolism, inflammation, and cancerous processes. Clustering of EAC samples according to published survival marker genes strongly suggests that IMP2 overexpressing samples show poor survival. Finally, IMP2 expression correlated with short survival in patients with EAC or esophageal squamous carcinoma. Our data indicate that IMP2 might be a useful prognostic marker for Barret’s esophagus and EAC.