This research article (Authors: P. Hudler, M. Simic, S. Frković Grazio, R. Komel) is an extension of the results published at the international conference From Arrays and Sequencing to Understanding Diseases, Ljubljana, 17th October 2014: paper “Analysis of candidate SNPs in selected segregation genes in gastric cancer” (Authors: M. Rogar, P. Hudler, N. Sodja, R. Komel); Book of Abstracts, p. 47 - http://cfgbc.mf.uni-lj.si/2014anniv9/AbstractBook_2014.pdf [COBISS.SI-ID 31641817]: Introduction: Gastric cancer is a common type of cancer; however the etiology of this heterogeneous disease is quite unknown. Carcinogenesis is very complex process involving genetic and epigenetic mechanisms. The main theme of novel genetic studies of gastric cancer is genomic instability which is broadly classified into microsatellite instability (MIN) and chromosomal instability (CIN) leading to aneuploidy. Kinases play pivotal roles throughout cellular division. From DNA damage and spindle assembly checkpoints before entering mitosis, to kinetochore and centrosome maturation and separation, to regulating the timing of entrance and exit of mitosis, mitotic kinases are essential for cellular integrity. Polymorphisms in genes which encode the mitotic kinases and/or their combinations may confer a higher relative contribution to the risk of developing cancer, but their lower penetrance makes identification more difficult. Aim: We would like to determine the association of polymorphisms and gastric cancer risk. There is a critical lack of information on the genetic backgrounds of cancer patients in Slovenia. We wish to continue and expand our pilot studies on the effect of polymorphisms in segregation genes in gastric cancer patients. Methods: We conducted a case-control study. The study included 164 patients with gastric cancer, which we collected in collaboration with the Department of Abdominal Surgery and the Department of Thoracic Surgery, University Medical Centre Ljubljana and Institute of Oncology Ljubljana. We used bioinformatics web tools in order to identify candidate SNPs in selected segregation genes, such as ZW10, CASC5, ESPL1 and TPX2. We performed SNP genotyping with TaqMan SNP assays. Results and conclusion: We found statistically significance between the tumor and the control group in polymorphism rs1185333 on the gene CASC5 (p = 0,022). According to our results we assume, that the polymorphism rs1185333 could have an impact on the development of gastric cancer. Interestingly, rs1185333 is statistically significant only in male population. Polymorphisms related to gastric cancer may be useful as potential biomarkers which could be used for detection of gastric cancer in early stages and could thus improve the prognosis of patients suffering from this type of cancer.
COBISS.SI-ID: 31641817
2DE in combination with MS has facilitated the discovery of several proteins with altered abundance in gastric cancer. While acidic and wide pH ranges have been widely investigated, analysis in the alkaline pH range has not been specifically performed in gastric cancer to date. In the present study we initially optimized the 2DE in alkaline pH range (pH 7-11) for gastric tissue samples. Using a modified lysis buffer, we analyzed pooled non-tumor and tumor samples for proteins with altered abundance in gastric adenocarcinoma (GA). We successfully identified 38 silver-stained spots as 24 different proteins. Four of these were chosen for investigation with immunoblotting on individual paired samples to determine whether the changes seen in 2DE represent the overall abundance of the protein or possibly only a single form. While mitochondrial trifunctional protein (MTP) subunits were decreased in 2DE gels, immunoblotting identified their overall abundance as being differently dysregulated: in the gastric tumor samples, the MTP- subunit (HADHA) was decreased, and the MTP- subunit (HADHB) was increased. On the other hand, heterogenous nuclear ribonucleoprotein M (HNRNPM) and galectin-4 (LGALS4) were increased in the gastric tumor samples both in 2DE and immunoblotting.
COBISS.SI-ID: 31019481
Novel proteomic methods are revealing the intricacy of the epigenetic landscape affecting gene regulation and improving our knowledge of the pathogenesis of complex diseases. Despite the enormous amount of data regarding epigenetic modifications present in DNA and histones, deciphering their biological relevance in the context of the disease and health is currently still an ongoing process. Here, we consider the relationship between epigenetic research in tumorigenesis and the prospect of knowledge transfer to clinical use, focusing primarily on the epigenetic histone post-translational modifications, which could be used as biomarkers. We additionally focus on the use of proteomic techniques in research and evaluate their usefulness in clinical setting.
COBISS.SI-ID: 31865305