Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.101
A. V. Sosnina, A. V. Vankhalsky, E. Mikhailova, T. A. Kunts, N. Varaksin, A. Autenshlyus
{"title":"P64: Effect of polyclonal activators on cytokine-producing capacity of blood immunocompetent cells in adenoma and adenocarcinoma of the stomach","authors":"A. V. Sosnina, A. V. Vankhalsky, E. Mikhailova, T. A. Kunts, N. Varaksin, A. Autenshlyus","doi":"10.1016/J.EJCSUP.2015.08.101","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.101","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"56-57"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.103
E. Starostina, D. Antonets, E. A. Borobova, L. Karpenko, A. Reguzova, O. Smirnova, A. Ilyichev, Bazhan Si
{"title":"P61: DNA-vaccines against melanoma: Design and investigation of antigenic properties","authors":"E. Starostina, D. Antonets, E. A. Borobova, L. Karpenko, A. Reguzova, O. Smirnova, A. Ilyichev, Bazhan Si","doi":"10.1016/J.EJCSUP.2015.08.103","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.103","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"57-58"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.036
S. Hofmann, I. Bure, A. Agaimy, A. Hartmann, F. Haller, E. Moskalev
{"title":"P152","authors":"S. Hofmann, I. Bure, A. Agaimy, A. Hartmann, F. Haller, E. Moskalev","doi":"10.1016/j.ejcsup.2015.08.036","DOIUrl":"10.1016/j.ejcsup.2015.08.036","url":null,"abstract":"<div><p>Aberrant alterations of DNA methylation patterns have been recognized as early and common events in oncogenesis emphasizing high therapeutic and preventive potential. Concurrent epigenetic silencing of multiple tumour suppressor genes has been reported in different tumours suggesting the existence of a directed program, whereby groups of genes are regulated by promoter methylation. The molecular bases of such a program remain largely unclear. Certain long non-coding RNAs (lncRNAs) have been recently identified that are responsible for target specificity of the histone modification complexes. It remains incompletely understood, however, if lncRNAs may play a role in patterning DNA methylation. In this study, we asked by using gastrointestinal stromal tumours as a model if an epigenetic related <em>HOX Antisense Intergenic RNA</em>, or <em>HOTAIR</em>, is involved in establishment of DNA methylation patterns. To this end, we first showed high up-regulation of <em>HOTAIR</em> in patient samples of high risk compared to low and intermediate risk groups (<em>n</em> <!-->=<!--> <!-->66, <em>p</em> <!-->=<!--> <!-->6.7<!--> <!-->×<!--> <!-->10<sup>−6</sup>), what is supported by the earlier reports on common carcinomas. Highest levels of <em>HOTAIR</em> endogenous expression were next detected also in cell lines GIST T1, GIST48b and GIST882. Stable knockdown of <em>HOTAIR</em> was achieved in GIST T1 and GIST48b cells by RNAi using lentiviral transduction. As expected epigenetic alterations due to <em>HOTAIR</em> knockdown could develop with a delay, genome-wide DNA methylation profiling was performed at passage 12 after the transduction on the Infinium HumanMethylation450 BeadChip platform in triplicates. DNA methylation data were analysed by an R package RnBeads. A total of 218 CpG sites got hypomethylated upon <em>HOTAIR</em> knockdown in GIST T1 and GIST48b cells (Δ<em>β</em> <!-->><!--> <!-->0.3, FDR<!--> <!--><<!--> <!-->0.05). These included potential tumour suppressors, transcription factors, tumour-specific antigens, genes related to angiogenesis or involved in metabolism. As confirmed by using bisulfite pyrosequencing for a representative locus, DNA methylation of 64% degree at promoter associated CpG sites of the potential tumour suppressor <em>RASSF1</em> was almost entirely erased upon <em>HOTAIR</em> knockdown in GIST T1 cell line with concomitant up-regulation detected by qRT-PCR. Concordant with earlier reports, <em>HOTAIR</em> knockdown led to reduced migration potential in GIST T1 cells. Taken together, the results suggest that <em>HOTAIR</em> is one of the factors involved in establishment of specific DNA methylation patterns in GIST. While the molecular mechanism remains to be determined, it is plausible to assume a recruitment of DNA methyltransferases by the Polycomb repressive complex 2, which target specificity is determined by <em>HOTAIR</em>. The results further suggest the feasibility of manipulating DNA methylat","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 20-21"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.048
D. Kokova , N. Dementeva , N. Cherdyntseva , A. Gratchev , Julia Kzhyshkowska
{"title":"P156","authors":"D. Kokova , N. Dementeva , N. Cherdyntseva , A. Gratchev , Julia Kzhyshkowska","doi":"10.1016/j.ejcsup.2015.08.048","DOIUrl":"10.1016/j.ejcsup.2015.08.048","url":null,"abstract":"<div><h3>Background</h3><p>Identification of DNA-based biomarkers of cancer cells is highly promising and rapidly developing direction that can advance early detection and therapy of malignancies. DNA adducts are felicitous markers of cancer, because their chemical structure is significantly different from that of mutated or methylated DNA, that allows to determine them with high precision using mass spectrometry. The aim of this work is to develop the methodology of sample preparation and its mass spectrometric analysis. Samples were prepared from the blood plasma and from the tumor tissue from lung cancer patients and from blood of healthy individuals.</p></div><div><h3>Materials and methods</h3><p>DNA was isolated from the blood plasma and tissue by using column method (BioSilica, Russia) The final yield from 1<!--> <!-->ml of blood was 100<!--> <!-->ng. DNA samples were subjected to acid hydrolysis (1<!--> <!-->M HCl) at 70<!--> <!-->°C. After 3<!--> <!-->h, the hydrolysis was stopped by cooling on ice for 5<!--> <!-->min and later on adding an equivalent amount of an alkali and a phosphate buffer solution (pH 7). To assess the extent of hydrolysis of the samples they were analysed by electrophoresis on a 1.2% agarose gel in Tris-acetate buffer. The samples were extracted at cartridge HF Bond Elut-C18 100<!--> <!-->mg, 1<!--> <!-->ml (Agilent Technologies, USA) and eluted in several fractions with a gradual increase of methanol in the eluent. Stream of nitrogen was applied to dry the extract. The samples were subjected to mass spectrometric analysis after pre-separation by UHLC Ultimate 3000 RS (Dionex, USA) in a column Dionex Acclaim RSLC 120 C18 (2.1<!--> <!-->×<!--> <!-->50<!--> <!-->mm 120<!--> <!-->A, 0.2<!--> <!-->μm) flow rate of 0.5<!--> <!-->ml/min using as eluents 0.1% solution of formic acid in water (A) and 0.1% solution of formic acid in atsetontrile (B). Elution was carried out in gradient mode: (%B): 0–3min (5%), 3–28min (5–95%), 28–30<!--> <!-->min (95%), 30–31<!--> <!-->min (95–5%), 31–35<!--> <!-->min (5%). Mass spectrometry was carried out on ESI-qTOF ultrahigh resolution Maxis 4G (Bruker, Germany) in the positive ion detection mode range 50–1000<!--> <!-->m/z, 2<!--> <!-->Hz with the following settings electrospray ion source: CV 3800<!--> <!-->V, Nebulizer gas 1<!--> <!-->bar, Dry Gas 8 l/min, Dry Temp: 200<!--> <!-->°C.</p></div><div><h3>Results</h3><p>It was found that the DNA which was cleaved with acid hydrolysis in the result contained single DNA bases. The samples were stable at 4<!--> <!-->°C for at least 7<!--> <!-->days. The optimal eluent for solid phase extraction of DNA is 80% solution of methanol in water. The number of DNA adducts was evaluated by the integrated value of the mass spectrometric response detector. It was shown that most amount of adducts 4-hydroxy-1-(3-pyridyl)-1- butanone and N3-(2-carbamoyl-2-hydroxyethyl)adenine was found in DNA samples derived from tumor tissue. The adduct N7-(2-carbamoyl-","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 27-28"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.058
A. Leshchenko , N. Matsenko
{"title":"P71","authors":"A. Leshchenko , N. Matsenko","doi":"10.1016/j.ejcsup.2015.08.058","DOIUrl":"10.1016/j.ejcsup.2015.08.058","url":null,"abstract":"<div><h3>Background</h3><p>Breast cancer is the most common cause of death from cancer among women aged 40–69<!--> <!-->years. According to WHO, about 1 million new cases of breast cancer are diagnosed annually worldwide, and nearly 500,000 die from it. In Russia, more than 55,000 women are diagnosed with breast cancer annually, and more than 22,000 die from it. Diagnosis and treatment of breast cancer is the primary and important social and medical problem.The increased expression of: (a) ER and PgR (70–75% of all cases of breast cancer) is an indication for hormone therapy, which is one of the simplest and most effective methods of systemic treatment of breast cancer; (b) receptor HER2/neu is a marker of highly aggressive form of breast cancer and indication for the use of targeted therapy Gertseptin; (c) proliferative factor Ki-67 reflects the ability of a tumor to metastasize.</p><p>Today, the “gold standard” of gene expression diagnostic of ER, PgR, HER2/neu and Ki-67 in breast cancer is immunohistochemistry (IHC) using foreign test systems (Ventana, Dako Inc, USA) . However, IHC diagnostics has some significant drawbacks. It leads up to 15–17% of cases of incorrect choice of drug therapy, which based on incorrect results of IHC studies. As a result, the significant group of patients do not receive effective treatment. Aim of the study Aim: the development a prototype of diagnostic test system for detection the receptor status of breast cancer, based on RT-PCR.</p></div><div><h3>Materials and methods</h3><p>Breast cancersamples consisted of 45 fresh-frozen tissue (FFT) samples of breast cancer (sites of malignant transformation and normal tissue from the same patients) and 59 FFPET sampleswere collected. All the samples had the IHC characteristic of receptor status of ER, PgR, HER2/neu and proliferation factor Ki-67 (Dako Inc., USA). Samples were submitted by SBIH NR “Novosibirsk Regional Oncology Center” (Novosibirsk, Russia). The experimental part of the study was divided into several stages: separation of mRNA from cells, obtaining cDNA (reverse transcription reaction), PCR in real-time and validation of the test system. Isolation of total RNA from FFT samples was performed using a set of “SV Total RNA Isolation system” according to the manufacturer’s instructions (Promega, USA). Isolation of total RNA from FFPET samples was performed using a set “ReliaPrep FFPE Total RNA Miniprep System” (Promega, USA) according to the manufacturer’s instructions. The concentration of total RNA was determined using a NanoDrop 1000 microspectrophotometer (Thermo Bioscience, USA) (RNA concentration were 15–660<!--> <!-->ng/ml).</p></div><div><h3>Results</h3><p>For the reverse transcription reaction (RT) and PCR, the main parameters were selected. For RT: RNA incubation time and temperature of the reaction, enzyme concentration in the reaction mix. For PCR: the amount of DNA template, the number of primers, the concentration of magny ions, the concentration","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 32-33"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54309629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.093
S. Shevchenko , L. Mostovich , N. Kolesnikov , L. Gulyaeva
{"title":"P82a","authors":"S. Shevchenko , L. Mostovich , N. Kolesnikov , L. Gulyaeva","doi":"10.1016/j.ejcsup.2015.08.093","DOIUrl":"10.1016/j.ejcsup.2015.08.093","url":null,"abstract":"<div><p>Preoperative differential diagnosis of benign thyroid nodules and thyroid cancer is an important issue of endocrinology. Preoperative identification of a tumor type allows a surgeon to determine an adequate surgical treatment and reduce complications. The cytological analysis of samples obtained by the fine-needle aspiration biopsy is limited in sensitivity and specificity and the core biopsy is not safe to be used in patients with thyroid nodes smaller than 2<!--> <!-->cm. The most promising area in the preoperative diagnosis of malignant tumors is molecular biomarkers, which can be used to determine the surgical treatment and indications for the target therapy. BRAF V600E is the most frequent genetic alteration in thyroid cancer. It activates the MAP-kinase pathway which causes changes in expression levels of extracellular matrix proteins and some of their receptors. Changes in the expression of integrin receptors and their ligands, such as osteopontin and thrombospondin-1, contribute to tumor cell proliferation and migration. The C-Jun pathway is also very important in pathogenesis of thyroid cancer. Changes in its activity can affect the expression of GSTP enzyme which participates in hormone metabolism. Altered MiRNA expression has been observed in a variety of cancer states allowing their potential use as cancer biomarkers.</p><p>The aim of this study was to evaluate integrins, angiogenic factors, GSTP and MiRNAs as potential biomarkers for the diagnosis and prognosis of thyroid cancer.</p><p>112 samples of papillary thyroid cancer (PTC) and 120 samples of benign nodular neoplasms were analyzed. The expression levels of the studied genes were determined by RT-PCR. The results were confirmed by immunohistochemical analysis. The BRAF V600E mutation was determined by allele-specific real-time PCR. The results showed that GSTP can be used for clinical settings as a cancer-specific marker for thyroid neoplasms with 83–88% sensitivity, 70–80% specificity and 76–84% diagnostic accuracy. Higher expression levels of integrins <em>α</em>2, <em>α</em>5, <em>α</em>v, <em>α</em>9, <em>β</em>1, <em>β</em>3 and IL-8, angiogenin, and VEGF were observed in malignant tumors in comparison with the normal thyroid tissue (<em>p</em> <!--><<!--> <!-->0.05). The BRAF V600E mutation was detected in 70% of all PTC cases. In the BRAF V600E positive PTC samples the levels of ITGA3 and ITGAV expression were higher than in the BRAF V600E negative ones (<em>p</em> <!--><<!--> <!-->0.05). The expression of miRNA 21, 221, 222, 155 was significantly increased in the cancer samples compared to the benign neoplasms. Thus, the studied molecular markers could be used for preoperative diagnosis of thyroid neoplasms and the treatment approach.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 52"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.096
O. Shpileva
{"title":"A139","authors":"O. Shpileva","doi":"10.1016/j.ejcsup.2015.08.096","DOIUrl":"10.1016/j.ejcsup.2015.08.096","url":null,"abstract":"<div><p>Cervical cancer is one of the most common female malignancies with incidence of 19.7 per 100,000 population in Russia in 2011 (Davydov, Aksel et al., 2011). Over 6000 women in Russia die of cervical cancer annually.</p><p>The cervical cancer incidence shows a tendency towards increasing rates among young women (Chissov, 2009). Tomsk region has been found to be the territory of increased cancer risk for cervical cancer. The age-standardized incidence rate is 1.87 times higher in Tomsk region than in Russia, being 20.40/0000 (Pisareva, Odintsova et al., 2012). The highest incidence of cervical cancer is observed in women aged 15–39<!--> <!-->years (Churuksaeva, Kolomiets, Shpileva, 2012). The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. Prevention of exposure to high risk HPV types by vaccination may prove to be the most efficient and logistically feasible preventive intervention for cervical cancer.</p><p>Epidemiological studies conducted at the Tomsk Cancer Research Institute have shown that the median age of patients with cervical intraepithelial neoplasia and cervical cancer is 39.9<!--> <!-->±<!--> <!-->8.5, and 89.5% of women are HPV-positive. Prevalence of high-grade squamous intraepithelial lesion (H-SIL) peaks between ages 25<!--> <!-->years and 30<!--> <!-->years.</p><p>The predominant HPV type in screened women of Tomsk region as well as worldwide is HPV-16, reaching peak incidence in women aged 36–40 years (74%). In the older age group (from 51 to 60<!--> <!-->years), HPV-18 is associated with 25% of cervical cancer cases. High prevalence of HPV-31 has been found in women under the age of 45 years with an incidence peak (17%) in the age group ⩽20<!--> <!-->years.</p><p>The geographical widespread data on HPV type-distribution are essential for estimating the impact of vaccines on cervical cancer and cervical screening programs. Immunization against HPV for young women aged between 9 and 26<!--> <!-->years, with a predominant age cohort 11–13<!--> <!-->years, was introduced in Tomsk region in 2010. The aim of the HPV immunization program is to protect females before they reach an age when the risk of HPV infection increases. A total of 627 girls were vaccinated, and 1653 doses of vaccines were injected. The three- dose schedule was given to 414 (66%) girls and 2-dose schedule to 198 (31.6%) girls. Vaccine safety assessment was carried out. Adverse effects were observed in 9.6% of cases and were mainly characterized by dizziness and pain at the injection site. Vaccination was well tolerated.</p><p>When calculating socio-economic feasibility of the proposed technology , not only the economic damage caused by the high mortality of women from cervical cancer, but also the cost for treatment of precancerous cervical lesions were taken into account, as out of 25 women with undetected CINII-III, 10 will develop cervical cancer. There have been calculated the estimated dam","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Pages 53-54"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54310144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/J.EJCSUP.2015.08.117
E. Voropaeva, T. Pospelova, Voevoda Mi, V. Maximov
{"title":"A36: The TP53 mutations in the Russian patients with de novo DLBCL","authors":"E. Voropaeva, T. Pospelova, Voevoda Mi, V. Maximov","doi":"10.1016/J.EJCSUP.2015.08.117","DOIUrl":"https://doi.org/10.1016/J.EJCSUP.2015.08.117","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"66"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.EJCSUP.2015.08.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54311003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ejc SupplementsPub Date : 2015-11-01DOI: 10.1016/j.ejcsup.2015.08.005
O. Bajenova, I. Evsyukov, S. O’Brien
{"title":"T125","authors":"O. Bajenova, I. Evsyukov, S. O’Brien","doi":"10.1016/j.ejcsup.2015.08.005","DOIUrl":"10.1016/j.ejcsup.2015.08.005","url":null,"abstract":"<div><p>Tumor markers play an important role in the identification of human malignancies. It has been shown that the carcinoembryonic antigen (CEA, CEACAM5) is a promoter of metastasis in epithelial cancers that is widely used as a clinical marker. The aim of this study is to elucidate the network of genes that are involved in the CEA-induced liver metastasis. Previously, we have shown that CEA is accumulated in the lungs and livers of rats by interacting with their macrophages. We identified and cloned a new gene (CEAR) for the CEA-binding protein, which is located on the surface of fixed liver macrophages, Kupffer cells (Bajenova et al, 2001). It has been shown that the interaction of CEA and CEAR proteins increases the production of IL-1, IL-10, IL-6, TNF-<em>α</em> cytokines (Thomas et al, 2011). This interaction changes the expression of liver adhesion molecules that enhances the survival of cancer cells to the liver. We also suggested that CEA synthesis by cancer cells may influence the E-cadherin adhesion junction complexes and have shown that CEA production violates the functional relationship between Ecadherin and its partners <em>α</em>-, <em>β</em>- and p120 catenin. A new type of interaction was discovered between the CEA and <em>β</em>-catenin and the increased amount of <em>β</em>-catenin in the nuclei of CEA producing cells. The data show that CEA production can cause the dissociation of cancer cells and trigger cancer progression. The CEA synthesis also alters splicing of p120 catenin protein and causes the release of soluble E-cadherin. Previously, CEA and epithelial E-cadherin were considered as independent tumor markers. Our data explain the correlation between the elevated levels of CEA and the increase in soluble E-cadherin in the progression of colorectal cancer (Bajenova et al, 2014).</p><p>We carried out a comparative transcriptome analysis of CEA-producing cell lines. The RNA transcriptome libraries were obtained and sequenced. By pairwise comparisons of CEA producing and non-producing cell lines using Cummerband program, we selected the set of genes (90 total genes) whose expression have been changed in the CEA-producing cell lines (overexpressed or downregulated). The biological processes that are linked to this differential gene expression were identified by Gene Set Enrichment Analysis (GSEA). In total, 8 significantly enriched GO terms related to the cellular components and biological processes were identified. Using KEGG and GO databases, we also identified the signaling pathways involved in the response to CEA. These findings have direct medical application, since they allow not only to establish the relationships between the existing biomarkers but also to discover the new ones. These biomarkers can be used for diagnosis and monitoring of metastatic carcinomas and for the drug development.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"13 1","pages":"Page 3"},"PeriodicalIF":0.0,"publicationDate":"2015-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.ejcsup.2015.08.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54308649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}