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001-es BibID:	BIBFORM083028
Első szerző:	Elek Zsuzsanna
Cím:	High Throughput Multiplex SNP-analysis In Chronic Obstructive Pulmonary Disease and Lung Cancer / Zsuzsanna Elek, Zsuzsanna Kovács, Gergely Keszler, Miklós Szabó, Eszter Csanky, Jane Luo, András Guttman, Zsolt Rónai
Dátum:	2020
ISSN:	1566-5240
Megjegyzések:	Background: A number of human inflammatory diseases and tumors have been shown to cause alterations in the glycosylation pattern of plasma proteins in a specific manner. These highly variable and versatile post-translational modifications finetune protein functions by influencing sorting, folding, enzyme activity and subcellular localization. However, relatively little is known about regulatory factors of this procedure and about the accurate causative connection between glycosylation and disease. Objective: The aim of the present study was to investigate whether certain single nucleotide polymorphisms (SNPs) in genes encoding glycosyltransferases and glycosidases could be associated with elevated risk for chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma. Methods: A total of 32 SNPs localized in genes related to N-glycosylation were selected for the association analysis. Polymorphisms with putative biological functions (missense or regulatory variants) were recruited. SNPs were genotyped by a TaqMan OpenArray platform. A single base extension-based method in combination with capillary gel electrophoresis was used for verification. Results: The TaqMan OpenArray approach provided accurate and reliable genotype data (global call rate: 94.9%, accuracy: 99.6%). No significant discrepancy was detected between the obtained and expected genotype frequency values (Hardy?Weinberg equilibrium) in the healthy control sample group in case of any SNP confirming reliable sampling and genotyping. Allele frequencies of the rs3944508 polymorphism localized in the 3' UTR of the MGAT5 gene significantly differed in the sample groups compared. Conclusion: Our results suggest that the rs34944508 SNP might modulate the risk for lung cancer by influencing the expression of MGAT5. This enzyme catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides, thus, increasing branching that is the characteristic of invasive malignancies.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk SNP single-base primer extension capillary gel electrophoresis TaqMan OpenArray lung adenocarcinoma COPD genetic association
Megjelenés:	Current Molecular Medicine. - 20 : 3 (2020), p. 185-193. -
További szerzők:	Kovács Zsuzsanna (1989-) Keszler Gergely Szabó Miklós (1980-) (tüdőgyógyász) Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Luo, Jane Guttman András (1954-) (vegyészmérnök) Rónai Zsolt
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001-es BibID:	BIBFORM092952
Első szerző:	Molnár Zsuzsanna
Cím:	Diabetes-specific Modulation of Peripheral Blood Gene Expression Signatures in Colorectal Cancer / Zsuzsanna Molnár, Zsófia Bánlaki, Anikó Somogyi, Zoltán Herold, Magdolna Herold, András Guttman, Zsolt Rónai, Gergely Keszler
Dátum:	2020
ISSN:	1566-5240
Megjegyzések:	Background: Type 2 diabetes (T2DM) and colorectal cancer (CRC) are both known to modulate gene expression patterns in peripheral blood leukocytes (PBLs). Objective: As T2DM has been shown to increase the incidence of CRC, we were prompted to check whether diabetes affects mRNA signatures in PBLs isolated from CRC patients. Methods: Twenty-two patients were recruited to the study and classified into four cohorts (healthy controls; T2DM; CRC; CRC and T2DM). Relative expression levels of 573 cell signaling gene transcripts were determined by reverse transcription real-time PCR assays run on low-density OpenArray platforms. Enrichment analysis was performed with the g:GOSt profiling tool to order differentially expressed genes into functional pathways. Results: 49 genes were found to be significantly up- or downregulated in tumorous diabetic individuals as compared to tumor-free diabetic controls, while 11 transcripts were differentially regulated in patients with CRC versus healthy, tumor-free and nondiabetic controls. Importantly, these gene sets were completely distinct, implying that diabetes exerts a profound influence on the transcription of signaling genes in CRC. The top 5 genes showing the most significant expression differences in both contexts were PCK2, MAPK9, CCND1, HMBS, TLR3 (p?0.0040) and CREBBP, PPIA, NFKBIL1, MDM2 and SELPLG (p?0.0121), respectively. Functional analysis revealed that most significantly affected pathways were cytokine, interleukin and PI3K/Akt/mTOR signaling cascades as well as mitotic regulation. Conclusion: We propose that differentially expressed genes listed above might be potential biomarkers of CRC and should be studied further on larger patient groups. Diabetes might promote colorectal carcinogenesis by impairing signaling pathways in PBLs.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Current Molecular Medicine. - 20 : 10 (2020), p. 773-780. -
További szerzők:	Bánlaki Zsófia Somogyi Anikó Herold Zoltán Herold Magdolna Guttman András (1954-) (vegyészmérnök) Rónai Zsolt Keszler Gergely
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