Expression profiles of histone modification genes in gastric cancer progression.

Gastric cancer (GC) development can be attributed to several risk factors including atrophic gastritis (AG), intestinal metaplasia (IM), and the presence of Helicobacter pylori (HP). Also, histone modification is an epigenetic mechanism that plays a pivotal role in GC carcinogenesis. In this preliminary study, we aimed to describe the expression profiles of histone modification in the AG, IM, and GC patient groups. A total of 80 patients with AG (n = 27), IM (n = 25), and GC (n = 28) with an additional 20 control subjects were included in the study. Expression profiles of three histone phosphorylation genes (PAK1, NEK6, and AURKA) and five histone deacetylation genes (HDACs 1, 2, 3, 5, and 7) were examined based on the results of Real Time qPCR method. It was observed that AURKA and HDAC2 genes were significantly overexpressed in all groups compared to the control (P < 0.05). In GC patients, overexpression of HDAC2 gene was detected in the absence of metastasis, and overexpression of AURKA, HDAC2, and NEK6 genes was detected in the presence of metastasis. When cancer involvements were compared, significant overexpression of the HDAC2 gene was noted in overall and corpus involvements (P < 0.05). In addition, overexpression of AURKA, NEK6, HDAC1, and HDAC2 genes and underexpression of HDAC5 gene were detected in the antrum involvement (P < 0.05). In conclusion, decreased expression of HDAC5 in GC is reported for the first time in this study, while supporting the existing literature in AURKA, NEK6, HDAC1, and HDAC2 up regulations during GC development.

Treatment of inflammatory bowel disease by leukocytapheresis.

Studies about leukocytapheresis have emerged with the need of search for alternatives to conventional treatment in inflammatory bowel diseases (IBD). Leukocytapheresis is a novel non-pharmacologic approach for active ulcerative colitis (UC) and Crohn's disease (CD), in which leukocytes are mechanically removed from the circulatory system. Patients with active IBD treated with leukocytapheresis using a Cellsorba E column between 2012 and 2015, were enrolled in Turkey. In our experience, the results of leukocytapheresis therapy in 6 patients with CD and 20 patients with active UC were overviewed. Leukocytapheresis (10 sessions for remission induction therapy, 6 sessions for maintenance therapy) was applied to the patients with their concomitant medications. Intensive leukocytapheresis (≥4 leukocytapheresis sessions within the first 2 weeks) was used in 30% patients with active severe UC. The overall clinical remission rate in patients with UC was 80%, and the mucosal healing rate was 65%. Patients were followed for an average of 24 months. It was observed that clinical remission has continued in 65% of patients with UC. Mild relapse was observed in 3 patients with UC during follow up period. In 5 patients with CD significant clinical remission was achieved except only one patient. Surgical needs were disappeared in 3 patients with obstructive type Crohn's disease. Adverse events were seen in only 4.3% of 416 sessions. Any concomitant medications did not increase the incidence of adverse events. Our results indicate that leukocytapheresis is efficacious in improving remission rates with excellent tolerability and safety in patients with IBD.

The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma.

Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. The objective of the present study is to investigate the alternations in the defined histone modification gene expression profiles in patients with CRAP and CRC. Histone modification enzyme key gene expressions of the CRC, CRAP, and control groups were evaluated and compared using the reverse transcription PCR (RT-PCR) array method. Gene expression analysis was performed in the CRAP group after dividing the patients into subgroups according to the polyp diameter, pathological results, and morphological parameters which are risk factors for developing CRC in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were significantly more overexpressed in CRC subjects compared to the controls (p < 0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed in the CRAP group compared to the controls (p < 0.005). There were no significant differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in correlation with the polyp diameter as they were more overexpressed in polyps with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and PAK1 genes can be used as predictive markers to decide the colonoscopic surveillance intervals after the polypectomy procedure especially in polyps with larger diameters.

Platelet, Mean Platelet Volume and Platelet Distribution Width Levels Might Be a Promising Marker for the Prediction of Disease Severity, Mucosal Healing and Steroid Dependence in Patients With Ulcerative Colitis.

BACKGROUND/AIMS: In this study, we aimed to determine the value of mean platelet (PLT) volume (MPV), PLT and PLT distribution width (PDW) levels as a marker in the prediction of mucosal healing (MH), steroid resistance (SR) and steroid dependence (SD) in newly diagnosed moderate and severely active patients with ulcerative colitis (UC), who did not receive medical treatment before. PATIENTS/METHODS: Two hundred forty-nine patients with severely or moderately active UC and 50 healthy subjects were enrolled in the study after retrospective analysis. Disease severity and MH of UC were determined according to the Mayo Score. According to the results of remission induction therapy, the patients were divided into two groups: Group 1; MH positive and Group 2; MH negative. UC patients with clinical remission (CR) but without MH were divided into two subgroups SD and non-SD during their follow-up. These two groups and subgroups were compared for variables. RESULTS: 42.6% of patients with UC had severe disease activation. 44.6% of patients with UC had pancolitis. After remission induction therapy, CR was observed in 84.3% of patients with UC. MH rate was 53.0%. SR rate was 15.7% and the SD rate was 16.1%. A strong positive correlation was observed between C reactive protein (CRP), PLT and Mayo score in the activation period (r=0.835 and p<0.001; r=0.883 and p<0.001; respectively). A strong negative correlation was observed between mean PLT volume (MPV), PDW levels and Mayo score (r=-0.905 and p<0.001; r=-0.805 and p<0.001; respectively). According to the receiver operating characteristic curve (ROC) analysis, PLT had a sensitivity of 42.4% and a specificity of 22.7% in the prediction of MH at a cut-off value of 266.5x103/µL. MPV had a sensitivity of 83.5% and a specificity of 73.5% in the prediction of MH at a cut-off value of 8.05 fL. PDW had a sensitivity of 88.6% and a specificity of 84.5% in the prediction of MH at a cut-off value of 2.95 fL. PLT was determined with 92.5% sensitivity and 86.8% specificity in the prediction of SD at a cut-off value of 287.0x103/µL. MPV had a sensitivity of 86.8% and a specificity of 67.5% in the prediction of SD at a cut-off value of 7.95 fL. PDW had a sensitivity of 73.7% and a specificity of 72.5% in the prediction of SD at a cut-off value of 12.55 fL. CONCLUSIONS: There was a positive correlation between PLT levels and Mayo score, and a negative correlation between Mayo score and MPV or PDW levels. We think that PLT, MPV and PDW levels may be promising markers in the evaluation of disease activation/remission and severity. We believe that PLT, MPV and PDW levels will be determinative especially in the exclusion of SD, for UC patients with CR but without MH.

Overexpressions of RHOA, CSNK1A1, DVL2, FZD8, and LRP5 genes enhance gastric cancer development in the presence of Helicobacter pylori.

BACKGROUND AND STUDY AIMS: Intestinal metaplasia (IM), and Helicobacter pylori (HP) infection can be shown as risk factors in the development of gastric cancer (GC). WNT signaling pathway plays a critical role in carcinogenesis. However, the literature studies are limited on the significance of this pathway for the transition from IM to GC. PATIENTS AND METHODS: We aimed to investigate the importance of the genes of WNT signaling pathways diagnostic and prognostic markers in the presence and absence of HP in conversion from IM to GC. 104 patients, (GC group n = 35, IM group n = 45, control group n = 25) were included in this case-control study. Expression of genes in WNT signalling were searched in study groups with qRT-PCR array and qRT-PCR method. Data were analysed using PCR array data analysis software. RESULTS: Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in the GC and IM groups compared to the control group (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was observed in patients with metastatic GC compared to patients with GC without metastasis (p < 0.05). It was found that the RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes were statistically significantly over-expressed in diffuse GC patients compared to non-diffuse GC patients (p < 0.05). Statistically significant overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes was detected in HP positive IM patients compared to HP negative IM patients (p < 0.05). CONCLUSION: Overexpression of RHOA, CSNK1A1, DVL2, FZD8 and LRP5 genes in IM may suggest that these genes are important markers in the development of IM and inflammation with HP. In addition, these genes are linked to tumor burden in the GC group. Consequently, we can conclude that these genes are poor prognosis biomarkers for GC and have the potential to be used as markers for future treatment monitoring.

Mean platelet volume can indicate dietary adherence and disease severity of celiac disease.

Objective: At present, there is no reliable indicator for dietary compliance and disease severity in patients with celiac disease (CD). The aim of this study is to evaluate mean platelet volume (MPV) level as a biomarker for detection of disease activation, dietary adherence, and assessment of disease severity. Methods: Eighty-one patients with CD and 50 healthy subjects were enrolled in this study. The diagnosis of CD was established by both positive antibodies against endomysium or gliadin and histopathological criteria (lymphocytic infiltration and total villous atrophy in duodenal biopsies). Results: MPV was observed to be significantly higher among CD patients when compared to healthy controls (8.14±0.26 fL vs. 7.82±0.29 fL and p=0.001). Overall dietary adherence rate was 72.8% (58/81 CD patients). After induction of a gluten-free diet, the MPV was significantly lower in the dietary adherent group than non-adherent patients (7.86±0.17 fL vs. 8.07±0.30 fL and p=0.001). The increase of MPV was correlated with Marsh classification (Marsh 3 active CD vs. Marsh 2 active CD vs. Marsh 1 active CD; 8.32±0.27 fL vs. 8.12±0.19 fL vs. 7.98±0.19 fL; p=0.004 and p=0.009). Conclusion: Based on these data, we believe that increased MPV can provide additional benefit to screening in patients with CD. It can indicate the activation of the disease and adherence to the diet.

Steroid Resistance/Dependence Might Be an Alarming Feature for Cytomegalovirus Infection Among Ulcerative Colitis Patients With Increased Disease Activity.

Background/Aims This study aimed to determine the prevalence of cytomegalovirus (CMV) infection among patients with moderate to severe active ulcerative colitis (UC) and to determine the risk factors for CMV infection according to the demographic features of these patients. Patients/Methods A total of 183 patients with severe or moderate active UC were enrolled in the study after retrospective analysis. The disease severity of UC was determined according to the Mayo Score. CMV infection was investigated by real-time quantitative polymerase chain reaction (PCR) and the immunohistochemical (IHC) staining method in colonic mucosal biopsies. Results CMV infection was diagnosed in 33.9% of patients with UC. UC patients diagnosed with CMV infection had significantly higher Mayo Score levels (9.68 vs 8.56 and p=0.001). The long-term presence of UC disease, steroid, azathioprine (AZA), and anti-tumor necrosis factor-alpha (anti-TNF-alpha) usage increased the risk of CMV infection (p=0.001 and odds ratio=1.168; p=0.001 and odds ratio=2.967; p=0.004 and odds ratio=2.953; p=0.003 and odds ratio=3.861, respectively). CMV infection increases the risk of developing steroid resistance or dependency (p=0.002 and odds ratio=3.147; p=0.002 and odds ratio=5.085, respectively). Post-treatment clinical remission and mucosal healing rates were higher in CMV-negative patients than in CMV-positive patients (99.2% vs 91.9%, p=0.018 and 86.8% vs 70.9%, p=0.015). A higher rate of need for colectomy had been found in patients with CMV infection (5 patients vs 1 patient; p=0.034 and odds ratio=10.526). Conclusions The presence of CMV infection increases the severity of the disease and worsens clinical outcomes, leading to adverse treatment outcomes. CMV infection increases the requirement for colectomy. The presence of steroids, immunosuppressives such as AZA, and anti-TNF-alpha usage increases the occurrence of CMV infection. CMV infection should be suspected in patients with moderate to severe UC activity.

Potential role of chromatin remodeling factor genes in atrophic gastritis/gastric cancer risk.

BACKGROUND/AIMS: Atrophic gastritis (AG), intestinal metaplasia (IM), and Helicobacter pylori (HP) are the risk factors for the development of gastric cancer (GC). Chromatin remodeling is one of the epigenetic mechanisms involved in the carcinogenesis of GC. The purpose of this study was to investigate the expression profiles of defined chromatin remodeling genes in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. MATERIALS AND METHODS: In total, 95 patients were included in the study. Patients were divided into 3 groups as: GC group (n=34), AG group (n=36), and control group (n=25). AG group was further divided into subgroups based on the presence of HP and IM in gastric mucosa. Chromatin remodeling gene expressions were analyzed using real-time PCR (RT-PCR) array in all groups. Data were evaluated using the RT-qPCR primer assay data analysis software. RESULTS: EED, CBX3, and MTA1 were more overexpressed, whereas ARID1A, ING5, and CBX7 were more underexpressed in the AG and GC groups compared with the controls. No significant differences were observed between the AG and GC groups concerning the expression of these 6 genes, although the fold change levels of these genes in the GC group were well above than in the AG group. EED, CBX3, and MTA1 were significantly more overexpressed in HP- and IM-positive AG subgroup compared with the HP- or IM-negative AG subgroup. CONCLUSION: In conclusion, our results provide an evidence of epigenetic alterations in AG. Expressions of EED, CBX3, MTA1, ARID1A, ING5, and CBX7 may be considered as promising markers to be used in GC screening for patients with AG.

Never in mitosis gene A-related kinase 6 and aurora kinase A: New gene biomarkers in the conversion from ulcerative colitis to colorectal cancer.

Ulcerative colitis (UC) is an important risk factor for colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. At present, there are no studies comparing histone modification patterns of UC and CRC in the literature. Therefore the aim of the present study was to investigate whether genes, particularly those involved in histone modification, have value in patient monitoring with regards to CRC development in UC. Key gene expressions of the histone modification enzyme were assessed and compared in CRC, UC and control groups using the RT-PCR array technique. Patients were divided into subgroups based on the extent and duration of the disease and inflammatory burden, which are considered risk factors for CRC development in UC patients. In UC and CRC groups, a significantly higher overexpression of the NEK6 and AURKA genes compared to the control group was identified. In addition, there was a significantly higher overexpression of HDAC1 and PAK1 genes in the UC group, and of HDAC1, HDAC7, PAK1 and AURKB genes in the CRC group. NEK6, AURKA, HDAC1 and PAK1 were significantly overexpressed in patients with a longer UC duration. Overexpression of AURKA and NEK6 genes was significantly more pronounced in UC patients with more extensive colon involvement. HDAC1, HDAC7, PAK1, NEK6, AURKA and AURKB are important diagnostic and prognostic markers involved in the carcinogenesis of CRC. HDAC1, PAK1, NEK6 and AURKA may be considered as diagnostic markers to be used in CRC screening for UC patients.