High γ-Radiation Sensitivity Is Associated with Increased Gastric Cancer Risk in a Chinese Han Population: A Case-Control Analysis

<div><p>Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of several malignancies, but not including gastric cancer. In this case-control study, radiation sensitivity as measured by chromatid breaks per cell (b/c) was examined in cultured peripheral blood lymphocytes (PBLs) from 517 patients with gastric cancer and 525 healthy controls. Our results showed that b/c values were significantly higher in cases than in controls (Mean [SD], 0.47 [0.20] <em>vs.</em> 0.34 [0.17]; <em>P</em><0.001). Using the 50^th percentile value for controls (0.34 b/c) as the cutoff point, unconditional logistic regression analysis revealed that γ–radiation-sensitive individuals were at significantly higher risk for gastric cancer (adjusted odds ratio [OR] 2.01, 95% confidence interval [CI] 1.49–3.13). Quartile stratification analysis indicated a dose-response relationship between γ-radiation sensitivity and gastric cancer risk (<em>P</em> for trend <0.001). When using the subjects in first quartile of b/c values as reference, the adjusted ORs and corresponding CIs for the subjects in second, third, and fourth quartiles were 1.48 (0.91–2.17), 2.42 (1.76–3.64), and 3.40 (2.11–5.29), respectively. The γ-radiation sensitivity was related to age and smoking status. In addition, a clear joint effect on cancer risk was found between γ-Radiation sensitivity and smoking status. The risk for ever smokers with high sensitivity was higher than those for never smokers with high sensitivity and ever smokers with low sensitivity (OR [CI], 4.67 [2.31–6.07] <em>vs.</em> 2.14 [1.40–3.06] vs. 2.42 [1.57–3.95], respectively). No significant interaction was found between both factors (<em>P</em> for interaction  = 0.42). We conclude that chromatid radiosensitivity is associated with gastric cancer susceptibility in a Chinese population.</p> </div

Joint effect of mutagen sensitivity and smoking in gastric cancer risk.

*<p>Adjusted for age, sex, H. pylori infection and drinking status.</p>#<p>Mutagen sensitivity was represented by number of chromatid breaks per cell (b/c).</p

Distribution of selected characteristics in gastric cancer cases and healthy controls.

<p>SD: standard deviation.</p>*<p>ever smokers only.</p>#<p>Mutagen sensitivity was represented by number of chromatid breaks per cell (b/c).</p

Comparison of mutagen sensitivity among different subgroups in gastric cancer cases or controls.

<p>SD: standard deviation.</p>a<p><i>p</i> values were determined by Student’s <i>t</i> test to assess the difference of mutagen sensitivity between two different subgroups in cases or controls.</p><p>Mutagen sensitivity was represented by number of chromatid breaks per cell (b/c).</p

DataSheet_1_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.docx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.</p

Table_2_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.xlsx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.</p

Table_3_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.xlsx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.</p

Quantitative Proteomics Analysis of Vitreous Humor from Diabetic Retinopathy Patients

Initial triggers for diabetic retinopathy (DR) are hyperglycemia-induced oxidative stress and advanced glycation end-products. The most pathological structural changes occur in retinal microvasculature, but the overall development of DR is multifactorial, with a complex interplay of microvascular, neurodegenerative, genetic/epigenetic, immunological, and secondary inflammation-related factors. Although several individual factors and pathways have been associated with retinopathy, a systems level understanding of the disease is lacking. To address this, we performed mass spectrometry based label-free quantitative proteomics analysis of 138 vitreous humor samples from patients with nonproliferative DR or the more severe proliferative form of the disease. Additionally, we analyzed samples from anti-VEGF (vascular endothelial growth factor) (bevacizumab)-treated patients from both groups. In our study, we identified 2482 and quantified the abundancy of 1351 vitreous proteins. Of these, the abundancy of 230 proteins was significantly higher in proliferative retinopathy compared with nonproliferative retinopathy. This specific subset of proteins was linked to inflammation, complement, and coagulation cascade proteins, protease inhibitors, apolipoproteins, immunoglobulins, and cellular adhesion molecules, reflecting the multifactorial nature of the disease. The identification of the key molecules of the disease is critical for the development of new therapeutic molecules and for the new use of existing drugs

Table_4_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.xlsx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.</p

Table_1_Genome-wide DNA methylation of Munro’s microabscess reveals the epigenetic regulation in the pathogenesis of psoriasis.xlsx

IntroductionMunro's microabscess is a typical pathological feature in the early psoriatic lesion, mainly characterized by the accumulation of neutrophils in the epidermis. DNA methylation microenvironment of Munro's microabscess and the crosstalk with transcription and its effect on neutrophils have not yet been revealed.MethodsPerformed genome-wide DNA methylation analysis and further differential methylation analysis of psoriatic skin lesions with and without Munro's microabscess from two batch samples consisting of 114 former samples in the discovery stage and 21 newly-collected samples in the validation stage. Utilized GO, MEME, and other tools to conduct downstream analysis on differentially methylated sites (DMSs). Correlation analysis of methylation level and transcriptome data was also conducted.ResultsWe observed 647 overlapping DMSs associated with Munro's microabscess. Subsequently, GO pathway analysis revealed that DNA methylation might affect the physical properties associated with skin cells through focal adhesion and cellsubstrate junction and was likely to recruit neutrophils in the epidermis. Via the MEME tool, used to investigate the possible binding transcription factors (TFs) of 20 motifs around the 647 DMSs, it was found that DNA methylation regulated the binding of AP1 family members and the recruitment of neutrophils in the epidermis through the TGF-beta pathway and the TH17 pathway. Meanwhile, combined with our earlier transcriptome data, we found DNA methylation would regulate the expressions of CFDP, SIRT6, SMG6, TRAPPC9, HSD17B7, and KIAA0415, indicating these genes would potentially promote the process of Munro's microabscess.DiscussionIn conclusion, DNA methylation may affect the course of psoriasis by regulating the progression of Munro's microabscess in psoriatic skin lesions.</p