目的:探讨全基因组关联研究(genome-wide association studies,GWAS)中识别的7个遗传位点与我国侗族人群2型糖尿病(type 2 diabetes mellitus,T2DM)的相关性。方法:在我国侗族人群中采用病例对照研究方法,利用多重PCR-SNa Pshot法对PARD...目的:探讨全基因组关联研究(genome-wide association studies,GWAS)中识别的7个遗传位点与我国侗族人群2型糖尿病(type 2 diabetes mellitus,T2DM)的相关性。方法:在我国侗族人群中采用病例对照研究方法,利用多重PCR-SNa Pshot法对PARD3B(rs849230),LOC729993(rs149228),EPHA4(rs16862811),HNT(rs3099797),PTPRD(rs17584499与rs649891),TOMM7(rs2240727)6个基因的7个位点进行基因分型。采用非条件二分类logistic回归方法分析每个多态位点与T2DM的相关性,利用边缘结构线性优势比模型进行基因与环境因素的交互作用分析。结果:本研究共包括209例T2DM患者与209例健康对照。TOMM7基因的rs2240727位点多态性与T2DM相关(对于每个拷贝的风险等位基因T,OR=1.50,P=0.004),且CT和TT基因型是T2DM的风险基因型,OR分别为2.07(95%CI:1.14~3.76)和2.75(95%CI:1.46~5.17),经Bonferroni多重比较校正后,上述结果仍然有意义(均P<0.05)。经调整年龄、性别、体质量指数(body mass index,BMI)后,rs2240727位点与T2DM仍有相关性(P<0.01)。交互作用分析结果表明:rs2240727位点与BMI、腰臀比(waist-hip ratio,WHR)、高血压、糖尿病家族史之间存在正交互作用,调整性别、年龄后,交互作用超额相对危险度(relative excess risk of interaction,RERI)分别为1.5430(95%CI:0.5797~2.5062),2.6520(95%CI:1.7516~3.5524),2.9131(95%CI:1.7959~4.0303),4.2062(95%CI:1.1686~8.2439),差异有统计学意义(均P<0.05)。结论:TOMM7基因的rs2240727位点遗传变异与我国侗族人群的T2DM相关,且与BMI、WHR、高血压和糖尿病家族史之间存在正交互作用。展开更多
目的探索G蛋白偶联受体81(G-protein coupled receptor 81,GPR81)和线粒体外膜异位酶20(translocase of the outer mitochondrial membrane member 20,TOMM20)在下咽癌中的功能及临床意义。方法选取30例经病理检查确诊为下咽鳞状细胞癌...目的探索G蛋白偶联受体81(G-protein coupled receptor 81,GPR81)和线粒体外膜异位酶20(translocase of the outer mitochondrial membrane member 20,TOMM20)在下咽癌中的功能及临床意义。方法选取30例经病理检查确诊为下咽鳞状细胞癌患者的下咽癌组织和癌旁组织,对患者临床资料进行统计学分析,并运用免疫组织化学方法检测GPR81和TOMM20在癌组织及癌旁组织中的表达。经特定浓度的顺铂诱导Fadu细胞,分别诱导0、12、24及48h,经Real-time PCR及Western Blot检测GPR81、TOMM20在mRNA和蛋白质水平的变化。采用流式细胞术检测顺铂刺激Fadu细胞后细胞凋亡情况。结果GPR81和TOMM20在下咽癌组织的表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。在下咽癌中,临床分期为I、II期的下咽癌中GPR81、TOMM20显著低于Ⅲ、IV期(P<0.05)。有淋巴结转移的下咽癌组织中GPR81、TOMM20的表达显著高于无淋巴结转移的下咽癌组织(P<0.05)。GPR81在中低分化的下咽癌中具有较高表达,在高分化下咽癌中表达较低,差异具有统计学意义(P<0.05)。不同分化程度的下咽癌中TOMM20的表达差异无统计学意义(P>0.05)。顺铂诱导Fadu细胞中GPR81及TOMM20的表达随时间呈现递减趋势,其mRNA水平及蛋白水平48h表达量与对照组相比,差异无统计学意义(P>0.05)。顺铂刺激的Fadu细胞中细胞凋亡数约为(11.35±0.87)%,对照组中细胞凋亡数为(18.68±0.33)%,两者经比较差异具有统计学意义(P<0.05)。结论GPR81、TOMM20可能与下咽癌的发生有关,二者可能参与了下咽癌化疗抵抗。因此能量代谢相关蛋白靶向研究或许是治疗侵袭性肿瘤的一个方向。展开更多
Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:...Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:Utilizing the TCGA and ICGC database,a prognostic stemness-related scores(SRS)for HCC through a combination of WGCNA and machine learning.Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups,identifying the key gene TOMM40L.qRT-PCR and IHC were employed to detect the expression level of TOMM40 L.Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in HCC.In vitro cell experiments explored the influence of TOMM40L on HCC cell progression and stemness.Results:The prognostic model SRS for HCC was developed and validated,incorporating four SRGs:EIF2B4,CDCA8,TCOF1,and TOMM40L.Distinct variations in tumor immune infiltration profiles and drug sensitivity were noted across different SRS subgroups.Elevated TOMM40L levels are notably detected in malignant tissues in contrast to adjacent tissues,with heightened TOMM40L expression correlating with unfavorable prognostic outcomes.In addition,knockdown of TOMM40L significantly inhibited cell progression and stemness.Conclusion:The newly constructed SRS model is a potential biomarker for assessing HCC prognosis,and the key gene TOMM40L exhibits oncogenic properties.展开更多
文摘目的:探讨全基因组关联研究(genome-wide association studies,GWAS)中识别的7个遗传位点与我国侗族人群2型糖尿病(type 2 diabetes mellitus,T2DM)的相关性。方法:在我国侗族人群中采用病例对照研究方法,利用多重PCR-SNa Pshot法对PARD3B(rs849230),LOC729993(rs149228),EPHA4(rs16862811),HNT(rs3099797),PTPRD(rs17584499与rs649891),TOMM7(rs2240727)6个基因的7个位点进行基因分型。采用非条件二分类logistic回归方法分析每个多态位点与T2DM的相关性,利用边缘结构线性优势比模型进行基因与环境因素的交互作用分析。结果:本研究共包括209例T2DM患者与209例健康对照。TOMM7基因的rs2240727位点多态性与T2DM相关(对于每个拷贝的风险等位基因T,OR=1.50,P=0.004),且CT和TT基因型是T2DM的风险基因型,OR分别为2.07(95%CI:1.14~3.76)和2.75(95%CI:1.46~5.17),经Bonferroni多重比较校正后,上述结果仍然有意义(均P<0.05)。经调整年龄、性别、体质量指数(body mass index,BMI)后,rs2240727位点与T2DM仍有相关性(P<0.01)。交互作用分析结果表明:rs2240727位点与BMI、腰臀比(waist-hip ratio,WHR)、高血压、糖尿病家族史之间存在正交互作用,调整性别、年龄后,交互作用超额相对危险度(relative excess risk of interaction,RERI)分别为1.5430(95%CI:0.5797~2.5062),2.6520(95%CI:1.7516~3.5524),2.9131(95%CI:1.7959~4.0303),4.2062(95%CI:1.1686~8.2439),差异有统计学意义(均P<0.05)。结论:TOMM7基因的rs2240727位点遗传变异与我国侗族人群的T2DM相关,且与BMI、WHR、高血压和糖尿病家族史之间存在正交互作用。
文摘目的探索G蛋白偶联受体81(G-protein coupled receptor 81,GPR81)和线粒体外膜异位酶20(translocase of the outer mitochondrial membrane member 20,TOMM20)在下咽癌中的功能及临床意义。方法选取30例经病理检查确诊为下咽鳞状细胞癌患者的下咽癌组织和癌旁组织,对患者临床资料进行统计学分析,并运用免疫组织化学方法检测GPR81和TOMM20在癌组织及癌旁组织中的表达。经特定浓度的顺铂诱导Fadu细胞,分别诱导0、12、24及48h,经Real-time PCR及Western Blot检测GPR81、TOMM20在mRNA和蛋白质水平的变化。采用流式细胞术检测顺铂刺激Fadu细胞后细胞凋亡情况。结果GPR81和TOMM20在下咽癌组织的表达水平显著高于癌旁组织,差异具有统计学意义(P<0.05)。在下咽癌中,临床分期为I、II期的下咽癌中GPR81、TOMM20显著低于Ⅲ、IV期(P<0.05)。有淋巴结转移的下咽癌组织中GPR81、TOMM20的表达显著高于无淋巴结转移的下咽癌组织(P<0.05)。GPR81在中低分化的下咽癌中具有较高表达,在高分化下咽癌中表达较低,差异具有统计学意义(P<0.05)。不同分化程度的下咽癌中TOMM20的表达差异无统计学意义(P>0.05)。顺铂诱导Fadu细胞中GPR81及TOMM20的表达随时间呈现递减趋势,其mRNA水平及蛋白水平48h表达量与对照组相比,差异无统计学意义(P>0.05)。顺铂刺激的Fadu细胞中细胞凋亡数约为(11.35±0.87)%,对照组中细胞凋亡数为(18.68±0.33)%,两者经比较差异具有统计学意义(P<0.05)。结论GPR81、TOMM20可能与下咽癌的发生有关,二者可能参与了下咽癌化疗抵抗。因此能量代谢相关蛋白靶向研究或许是治疗侵袭性肿瘤的一个方向。
基金supported by the National Natural Science Foundation of China(No.82370608)Natural Science Foundation of Anhui Province(No.2208085MH204)+5 种基金Natural Science Foundation of Education Department of Anhui Province(No.2022AH040160)Anhui Provincial Special Fund for Clinical Medical Research Transformation(No.202304295107020040)Suzhou Health Commission“Suzhou Health Young Talent”National Mentor Training Program(No.Qngg2023046)Kunshan Social Development Science and Technology Special Fund(No.KS1719)New Coronavirus Pneumonia Research Project of Kunshan First People’s Hospital(First Batch,No.XGF202018)Kunshan First People’s Hospital Medical and Health Science and Technology Innovation Special Project(No.KETDCX202424).
文摘Aims:The aim of this study is to develop a prognostic model for hepatocellular carcinoma(HCC)using stemness-related genes(SRGs),while also pinpointing and validating pivotal genes associated with this process.Methods:Utilizing the TCGA and ICGC database,a prognostic stemness-related scores(SRS)for HCC through a combination of WGCNA and machine learning.Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups,identifying the key gene TOMM40L.qRT-PCR and IHC were employed to detect the expression level of TOMM40 L.Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in HCC.In vitro cell experiments explored the influence of TOMM40L on HCC cell progression and stemness.Results:The prognostic model SRS for HCC was developed and validated,incorporating four SRGs:EIF2B4,CDCA8,TCOF1,and TOMM40L.Distinct variations in tumor immune infiltration profiles and drug sensitivity were noted across different SRS subgroups.Elevated TOMM40L levels are notably detected in malignant tissues in contrast to adjacent tissues,with heightened TOMM40L expression correlating with unfavorable prognostic outcomes.In addition,knockdown of TOMM40L significantly inhibited cell progression and stemness.Conclusion:The newly constructed SRS model is a potential biomarker for assessing HCC prognosis,and the key gene TOMM40L exhibits oncogenic properties.
