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MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer:Current insights and future perspectives

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World Journal of Gastroenterology 2018年第30期24卷 3313-3329页

作者： alexander link juozas kupcinskas Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke University Institute for Digestive Research and Department of Gastroenterology Lithuanian University of Health Sciences

Non-invasive diagnostic biomarkers may contribute to an early identification of gastric cancer(GC) and improve the clinical ***,no sensitive and specific screening biomarkers are available yet and the currently available approaches are limited by the nature of the *** is a heterogenic disease with various distinct genetic and epigenetic events that occur during the multifactorial cascade of *** RNAs(mi RNAs) are commonly deregulated in gastric mucosa during the Helicobacter pylori infection and in stepwise manner from chronic gastritis,through preneoplastic conditions such as atrophic gastritis and intestinal metaplasia,to early dysplasia and invasive *** of mi RNAs in blood in 2008 led to a great interest on mi RNA-based diagnostic,prognostic biomarkers in *** this review,we provide the most recent systematic review on the existing studies related to mi RNAs as diagnostic biomarkers for ***,we systematically evaluate 75 studies related to differential expression of circulating mi RNAs in GC patients and provide novel view on various heterogenic aspects of the existing data and summarize the methodological ***,we highlight several important aspects crucial to improve the future translational and clinical research in the field.

关键词： microRNA biomarkers screening stomach gastric cancer systematic review blood serum plasma

Comparison of genomic and transcriptional microbiome analysis in gastric cancer patients and healthy individuals

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World Journal of Gastroenterology 2023年第7期29卷 1202-1218页

作者： Darja Nikitina Konrad Lehr Ramiro Vilchez-Vargas Laimas Virginijus Jonaitis Mindaugas Urba juozas kupcinskas Jurgita Skieceviciene alexander link Institute for Digestive Research Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke University HospitalMagdeburg 39120Germany Department of Gastroenterology Lithuanian University of Health SciencesKaunas 44307Lithuania

BACKGROUND Helicobacter pylori and the stomach microbiome play a crucial role in gastric carcinogenesis,and detailed characterization of the microbiome is necessary for a better understanding of the pathophysiology of the *** are two common modalities for microbiome analysis:DNA(16S rRNA gene)and RNA(16S rRNA transcript)*** implications from the use of one or another sequencing approach on the characterization and comparability of the mucosal microbiome in gastric cancer(GC)are poorly *** To characterize the microbiota of GC using 16S rRNA gene and its transcript and determine difference in the bacterial *** In this study,316 DNA and RNA samples extracted from 105 individual stomach biopsies were *** study cohort consisted of 29 healthy control individuals and 76 patients with *** tissue biopsy samples were collected from damaged mucosa and healthy mucosa at least 5 cm from the tumor *** the controls,healthy stomach mucosa biopsies were *** all biopsies RNA and DNA were *** was reverse transcribed into cDNA.V1-V2 region of bacterial 16S rRNA gene from all samples were amplified and sequenced on an Illumina MiSeq ***-Curtis algorithm was used to construct sample-similarity matrices abundances of taxonomic ranks in each sample *** significant differences between groups permutational multivariate analysis of variance and Mann-Whitney test followed by false-discovery rate test were *** Microbial analysis revealed that only a portion of phylotypes(18%-30%)overlapped between microbial profiles obtained from DNA and RNA *** analysis revealed differences between GC and controls depending on the chosen modality,identifying 17 genera at the DNA level and 27 genera at the RNA *** of those bacteria were found to be different from the control group at both *** key taxa showed congruent results in various tests used;however,differences in 7 b

关键词： Gastric cancer Microbiome Helicobacter pylori 16S rRNA gene 16S rRNA transcript 16S rDNA

Plasma Nogo-A and placental growth factor levels are associated with portal hypertension in patients with liver cirrhosis

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World Journal of Gastroenterology 2019年第23期25卷 2935-2946页

作者： Sigita Gelman Violeta Salteniene Andrius Pranculis Jurgita Skieceviciene Romanas Zykus Dalius Petrauskas Limas kupcinskas Ali Canbay alexander link juozas kupcinskas Department of Gastroenterology Medical AcademyLithuanian University of Health SciencesKaunas 44307Lithuania Institute for Digestive Research Medical AcademyLithuanian University of Health SciencesKaunas 44307Lithuania Department of Radiology Medical AcademyLithuanian University of Health SciencesKaunas 44307Lithuania Institute for Digestive Research and Department of Gastroenterology Medical AcademyLithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Hepatology and Infectious Diseases Otto-von-Guericke UniversityMagdeburg 39106Germany

BACKGROUND Clinically significant portal hypertension(CSPH) and severe portal hypertension(SPH) increase the risk for decompensation and life-threatening complications in liver cirrhosis. Pathologic angiogenesis might contribute to the formation of these conditions. Placental growth factor(PlGF) and Nogo-A protein are biomarkers of pathological angiogenesis, but data on their role in liver cirrhosis and portal hypertension is *** To determine plasma levels of PlGF and Nogo-A in patients with liver cirrhosis,CSPH, SPH and potential to predict portal *** A cohort of 122 patients with hepatitis C virus and/or alcohol-induced liver cirrhosis with characterized hepatic venous pressure gradient(HVPG) were included in the study. Demographic data, medical history, Child-Turcotte-Pugh and Model of End Stage liver disease score, clinical chemistry, liver stiffnessvalues were recorded on the day of the procedure prior HVPG measurement. The degree of portal hypertension was determined by the invasive HVPG measurement. Nogo-A and PlGF plasma levels were evaluated using enzyme linked immunosorbent assay. The control group consisted of 30 healthy age-and sex-matched *** Peripheral PlGF levels were higher and Nogo-A levels were lower in patients with liver cirrhosis(23.20 vs 9.85;P < 0.0001 and 2.19 vs 3.12;P = 0.004 respectively). There was a positive linear correlation between peripheral levels of PlGF and HVPG(r = 0.338, P = 0.001) and negative linear correlation between the peripheral Nogo-A levels and HVPG(r =-0.267, P = 0.007). PlGF levels were higher in CSPH and SPH(P = 0.006;P < 0.0001) whereas Nogo-A levels were lower(P = 0.01;P < 0.033). Area under the curve for the diagnosis of CSPH for PlGF was 0.68(P = 0.003) and for Nogo-A-0.67(P = 0.01);for SPH 0.714(P <0.0001) and 0.65(P = 0.014) respectively. PlGF levels were higher and Nogo-A levels were lower in patients with esophageal varices(P < 0.05). PlGF cut-off value of 25 pg/mL dist

关键词： Liver cirrhosis Portal hypertension Angiogenesis Placental growth factor Nogo-A Hepatic venous pressure gradient

Polymorphisms of micro RNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer

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World Journal of Gastroenterology 2017年第19期23卷 3480-3487页

作者： Vytenis Petkevicius Violeta Salteniene Simonas Juzenas Thomas Wex alexander link Marcis Leja Ruta Steponaitiene Jurgita Skieceviciene Limas kupcinskas Laimas Jonaitis Gediminas Kiudelis Peter Malfertheiner juozas kupcinskas Department of Gastroenterology Lithuanian University of Health Sciences Institute for Digestive Research Lithuanian University of Health Sciences Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke University Medical Laboratory for Clinical Chemistry Microbiology and Infectious DiseasesDepartment of MolecularGeneticsOtto-von-Guericke University Institute for Clinical and Preventive Medicine University of Latvia Faculty of Medicine University of Latvia Riga East University Hospital

AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European *** Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and *** were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous *** cancer(GC)patients had histopathological verification of gastric *** DNA was extracted using salting out method from peripheral blood mononuclear ***12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain *** between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of *** We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR *** frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,Plinked with the presence of GC.

关键词： Gastric cancer miRNA Target genes Single-nucleotide polymorphisms

Atrophic gastritis and gastric cancer tissue miRNome analysis reveals hsa-miR-129-1 and hsa-miR-196a as potential early diagnostic biomarkers

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World Journal of Gastroenterology 2022年第6期28卷 653-664页

作者： Greta Varkalaite Evelina Vaitkeviciute Ruta Inciuraite Violeta Salteniene Simonas Juzenas Vytenis Petkevicius Rita Gudaityte Antanas Mickevicius alexander link Limas kupcinskas Marcis Leja juozas kupcinskas Jurgita Skieceviciene Institute for Digestive Research Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Surgery Lithuanian University of Health SciencesKaunas 44307Lithuania Department of Gastroenterology Hepatology and Infectious DiseasesOttovon-Guericke University HospitalMagdeburg 39120Germany Institute of Clinical and Preventive Medicine&Faculty of Medicine University of LatviaRiga 1586Latvia

BACKGROUND Gastric cancer(GC)is one of the most frequently diagnosed tumor *** most cases,GC develops in a stepwise manner from chronic gastritis or atrophic gastritis(AG)to *** of the major issues in clinical settings of GC is diagnosis at advanced disease stages resulting in poor *** RNAs(mi RNAs)are small noncoding molecules that play an essential role in a variety of fundamental biological ***,clinical potential of mi RNA profiling in the gastric cancerogenesis,especially in premalignant GC cases,remains *** To evaluate the AG and GC tissue mi RNomes and identify specific mi RNAs’potential for clinical applications(e.g.,non-invasive diagnostics).METHODS Study included a total of 125 subjects:Controls(CON),AG,and GC *** study subjects were recruited at the Departments of Surgery or Gastroenterology,Hospital of Lithuanian University of Health Sciences and divided into the profiling(n=60)and validation(n=65)*** RNA isolated from tissue samples was used for preparation of small RNA sequencing libraries and profiled using next-generation sequencing(NGS).Based on NGS data,deregulated mi RNAs hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p were analyzed in plasma samples of independent cohort consisting of CON,AG,and GC *** level of hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p was determined using the quantitative real-time polymerase chain reaction and 2-ΔΔCt *** Results of tissue analysis revealed 20 differentially expressed mi RNAs in AG group compared to CON group,129 deregulated mi RNAs in GC compared to CON,and 99 altered mi RNAs comparing GC and AG *** 2 mi RNAs(hsa-mi R-129-1-3 p and hsa-mi R-196 a-5 p)were identified to be step-wise deregulated in healthy-premalignant-malignant *** under the curve(AUC)-receiver operating characteristic analysis revealed that expression level of hsa-mi R-196 a-5 p is significant for discrimination of CON vs AG,CON vs GC and A

关键词： Gastric cancer Atrophic gastritis Tumorigenesis Helicobacter pylori MicroRNAs Biomarkers