为了解绵羊热休克蛋白1L(heat shock protein family A member 1 like,HSPA1L)基因及其编码产物的基本结构和生物学特征,给绵羊的抗热应激和免疫等方面的研究提供依据,利用生物信息学数据库及软件对绵羊HSPA1L基因进行生物信息学分析。...为了解绵羊热休克蛋白1L(heat shock protein family A member 1 like,HSPA1L)基因及其编码产物的基本结构和生物学特征,给绵羊的抗热应激和免疫等方面的研究提供依据,利用生物信息学数据库及软件对绵羊HSPA1L基因进行生物信息学分析。结果表明,该基因最大长度的ORF有1926 bp,编码641个氨基酸序列。其编码的蛋白质分子式为C_(3094)H_(4985)N_(859)O_(969)S_(20),理论等电点为5.89,不稳定指数为32.56。该蛋白无信号肽和跨膜结构,为非分泌性蛋白,主要在细胞质中发挥生物学作用。无规则卷曲是构成该蛋白二级结构和三级结构的主要方式。展开更多
Background Lung squamous cell carcinoma(LUSC)is a major subtype of non-small cell lung cancer with a high mortality rate.Identifying causal plasma proteins associated with LUSC could provide new insights into the path...Background Lung squamous cell carcinoma(LUSC)is a major subtype of non-small cell lung cancer with a high mortality rate.Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets.This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization(MR)and colocalization analyses.Methods Proteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics.Summary-level data for LUSC were obtained from the ILCCO Consortium,the FinnGen study,and a separate GWAS study.A total of 1,046 shared protein quantitative trait loci(pQTLs)were analyzed.Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations.Results MR analysis identified six plasma proteins associated with LUSC risk:HSPA1L,PCSK7,POLI,SPINK2,TCL1A,and VARS.HSPA1L(OR=0.47;95%CI:0.34–0.65;P=4.89×10^(–6)),SPINK2(OR=0.68;95%CI:0.58–0.80;P=3.17×10^(–6)),and VARS(OR=0.44;95%CI:0.31–0.63;P=5.94×10^(–6))were associated with a decreased risk of LUSC.Conversely,PCSK7(OR=1.37;95%CI:1.21–1.56;P=1.40×10^(–6)),POLI(OR=4.50;95%CI:2.25–9.00;P=2.13×10–5),and TCL1A(OR=1.72;95%CI:1.34–2.21;P=1.89×10–5)were associated with an increased risk.The SMR analysis and HEIDI test confirmed the robustness of these associations.HSPA1L,SPINK2,and VARS showed significant inverse associations,with strong colocalization evidence for TCL1A(PPH4=0.817).Conclusions This study identified six plasma proteins potentially causal for LUSC risk.HSPA1L,SPINK2,and VARS are associated with decreased risk,while PCSK7,POLI,and TCL1A are linked to increased risk.These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention.展开更多
文摘为了解绵羊热休克蛋白1L(heat shock protein family A member 1 like,HSPA1L)基因及其编码产物的基本结构和生物学特征,给绵羊的抗热应激和免疫等方面的研究提供依据,利用生物信息学数据库及软件对绵羊HSPA1L基因进行生物信息学分析。结果表明,该基因最大长度的ORF有1926 bp,编码641个氨基酸序列。其编码的蛋白质分子式为C_(3094)H_(4985)N_(859)O_(969)S_(20),理论等电点为5.89,不稳定指数为32.56。该蛋白无信号肽和跨膜结构,为非分泌性蛋白,主要在细胞质中发挥生物学作用。无规则卷曲是构成该蛋白二级结构和三级结构的主要方式。
基金supported by The Medical Engineering Cross Research Funding of Shanghai Jiaotong University"Star of Jiaotong University"Program(24X010301595).
文摘Background Lung squamous cell carcinoma(LUSC)is a major subtype of non-small cell lung cancer with a high mortality rate.Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets.This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization(MR)and colocalization analyses.Methods Proteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics.Summary-level data for LUSC were obtained from the ILCCO Consortium,the FinnGen study,and a separate GWAS study.A total of 1,046 shared protein quantitative trait loci(pQTLs)were analyzed.Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations.Results MR analysis identified six plasma proteins associated with LUSC risk:HSPA1L,PCSK7,POLI,SPINK2,TCL1A,and VARS.HSPA1L(OR=0.47;95%CI:0.34–0.65;P=4.89×10^(–6)),SPINK2(OR=0.68;95%CI:0.58–0.80;P=3.17×10^(–6)),and VARS(OR=0.44;95%CI:0.31–0.63;P=5.94×10^(–6))were associated with a decreased risk of LUSC.Conversely,PCSK7(OR=1.37;95%CI:1.21–1.56;P=1.40×10^(–6)),POLI(OR=4.50;95%CI:2.25–9.00;P=2.13×10–5),and TCL1A(OR=1.72;95%CI:1.34–2.21;P=1.89×10–5)were associated with an increased risk.The SMR analysis and HEIDI test confirmed the robustness of these associations.HSPA1L,SPINK2,and VARS showed significant inverse associations,with strong colocalization evidence for TCL1A(PPH4=0.817).Conclusions This study identified six plasma proteins potentially causal for LUSC risk.HSPA1L,SPINK2,and VARS are associated with decreased risk,while PCSK7,POLI,and TCL1A are linked to increased risk.These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention.
