TY - JOUR A1 - Kunz, Meik A1 - Wolf, Beat A1 - Schulze, Harald A1 - Atlan, David A1 - Walles, Thorsten A1 - Walles, Heike A1 - Dandekar, Thomas T1 - Non-Coding RNAs in Lung Cancer: Contribution of Bioinformatics Analysis to the Development of Non-Invasive Diagnostic Tools JF - Genes N2 - Lung cancer is currently the leading cause of cancer related mortality due to late diagnosis and limited treatment intervention. Non-coding RNAs are not translated into proteins and have emerged as fundamental regulators of gene expression. Recent studies reported that microRNAs and long non-coding RNAs are involved in lung cancer development and progression. Moreover, they appear as new promising non-invasive biomarkers for early lung cancer diagnosis. Here, we highlight their potential as biomarker in lung cancer and present how bioinformatics can contribute to the development of non-invasive diagnostic tools. For this, we discuss several bioinformatics algorithms and software tools for a comprehensive understanding and functional characterization of microRNAs and long non-coding RNAs. KW - lung cancer KW - non-invasive biomarkers KW - miRNAs KW - lncRNAs KW - bioinformatics KW - early diagnosis KW - algorithm Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147990 VL - 8 IS - 1 ER - TY - THES A1 - Krauss, Eva T1 - Analyse der Expression von MAGE-A-Antigenen in Präkursorläsionen und manifesten Tumoren des oralen Plattenepithelkarzinoms T1 - Analysis of the expression of MAGE-A-antigens in oral precancerous lesions and neoplasm of the oral squamous cell carcinoma N2 - Orale Plattenepithelkarzinome entwickeln sich häufig aus Präkanzerosen. Trotz der Frühdiagnostik ist es für den Kliniker und den Pathologen meist schwierig eine Präkanzerose, die zur Entartung neigt, rechtzeitig als solche zu erkennen. MAGE-A-Antigene sind Tumorantigene, die nur in malignen Zellen vorkommen. Diese Antigene können dazu dienen, Karzinome früher als solche zu erkennen. Das Ziel dieser Studie war, diese Hypothese zu bestätigen, indem gutartige, präkanzeröse und karzinomatöse Veränderung untersucht wurden. Dazu wurden retrospektiv Biopsien der oralen Schleimhaut (orale Ulzera, Epulitiden, follikuläre Zysten, Lichen planus, Leukolakien, epitheliale Dysplasien und Carcinomata in situ) untersucht. Diese wurden immunhistochemisch mit dem polyklonalen Antikörper MAGE-A 57B angefärbt. Dabei stellte sich heraus, dass MAGE-A-Antigene nicht in gutartigen Veränderungen vorkommen, jedoch zu 33-65% in präkanzerösen und malignen Läsionen. Ein weiteres Ziel umfasste die Untersuchung der kritischen Randbereiche. Hier wurde bei den positv gefärbten Präparaten eine eindeutige Grenze zwischen benigner und maligner Schleimhaut durch die Anfärbung mit mAb-57B sichtbar. N2 - Oral squamous cell carcinoma develops often out of predamaged oral mucosa. Despite of early diagnostic it is difficult for the physician and pathologist to distinguish between precancerous and cancerous lesions. MAGE-A antigens are tumor antigens that are found solely in malignant transformed cells. So these antigens might be useful in detecting cancerous lesions. The aim of this study was to verify this hypothesis by comparing MAGE-A expression in benign, precancerous, and cancerous lesions of the oral mucosa. Therefore we retrospectively examined biopsies of different oral lesions (oral ulcers, dental follicles, epulises, oral lichen planus, leukoplakia, epithelial dysplasias and carcinomas in situ). The lesions were immunohistochemically stained with the poly-MAGE-A antibody 57B. MAGE-A antigens were nearly not detectable via immunohistochemistry in benign lesions of the oral mucosa. The staining rate of precancerous lesions or malignant lesions alternated from 33% to 65%. The second aim concerned the margins of the lesions. In positive stained lesions the antibody could make it easier to detect the margin between benign and malignant lesions. KW - Präkanzerose KW - Leukoplakie KW - Lichen ruber planus KW - Plattenepithelcarcinom KW - Frühdiagnostik KW - MAGE-A-Antigene KW - Cancer/Testis Antigene KW - Leukoplakia KW - Lichen planus KW - Oral squamous cell carcinoma KW - Oral mucosa KW - Oral Precancer KW - MAGE-A-antigens KW - early diagnosis Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-66188 ER - TY - JOUR A1 - Molochnikov, Leonid A1 - Rabey, Jose M. A1 - Dobronevsky, Evgenya A1 - Bonuccelli, Ubaldo A1 - Ceravolo, Roberto A1 - Frosini, Daniela A1 - Grünblatt, Edna A1 - Riederer, Peter A1 - Jacob, Christian A1 - Aharon-Peretz, Judith A1 - Bashenko, Yulia A1 - Youdim, Moussa B. H. A1 - Mandel, Silvia A. T1 - A molecular signature in blood identifies early Parkinson's disease JF - Molecular Neurodegeneration N2 - Background: The search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD. Results: The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n = 29). Conclusions: The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder. KW - cerebrospina KW - magnetic-resonance-spectroscopy KW - protein KW - biomarkers KW - E3 ubiquitin ligase KW - SCF KW - SKP1 KW - heat shock protein Hsc-70 KW - early diagnosis KW - fluid KW - alpha-synuclein KW - dehydrogenases KW - Alzheimer's disease KW - sporadic Parkinson's disease KW - blood biomarker KW - CSF KW - multiple system atrophy KW - clinical diagnosis KW - substantia nigra KW - gene expression Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134508 VL - 7 IS - 26 ER -