Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between geneti...Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.展开更多
Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide ...Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.展开更多
The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes wo...The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.展开更多
基金funded by the National Key R&D Program of China(Grant Nos.2018YFC1313100 and 2018YFC1313102)the National Natural Science Foundation of China(Grant No.81773539)+1 种基金Collaborative Innovation Center for Cancer Personalized Medicinethe Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.
基金The current study was supported by the National Natural Science Foundation of China(Grant Nos.82130096 and 82373537)Collaborative Innovation Center for Cancer Personalized Medicine and Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
基金the National Key R&D Program of China(Grants No.2018YFC1313100 and No.2018YFC1313102)the National Natural Science Foundation of China(Grants No.81773538 and No.81773539)Collaborative Innovation Center for Cancer Personalized Medicine,and the Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.
