双硫死亡状态与肿瘤患者炎症反应、免疫抑制和药物敏感性相关。然而,其在结直肠癌诊疗中的价值尚不清楚。基于此,研究使用单细胞测序数据和细胞特异性标记基因分析双硫死亡与不同结直肠癌细胞类型的相关性,发现结直肠癌高双硫死亡区域...双硫死亡状态与肿瘤患者炎症反应、免疫抑制和药物敏感性相关。然而,其在结直肠癌诊疗中的价值尚不清楚。基于此,研究使用单细胞测序数据和细胞特异性标记基因分析双硫死亡与不同结直肠癌细胞类型的相关性,发现结直肠癌高双硫死亡区域集中于上皮类细胞中。结合程序性细胞死亡蛋白1抑制剂治疗结直肠癌患者的肿瘤组织差异基因表达数据,建立双硫死亡相关预后模型分析发现,高双硫死亡水平结直肠癌患者风险较低,免疫治疗敏感性高。结合空间转录物组学分析发现,双硫死亡相关基因泛醇细胞色素C还原酶核心蛋白Ⅰ(ubiquinol-cytochrome c reductase core protein 1,UQCRC1)是潜在的结直肠癌诊疗靶点,其表达在上皮类结直肠癌细胞中较高,与结直肠癌免疫浸润区域存在共定位。进一步的生信分析和实验检测显示,UQCRC1在结直肠癌组织中低表达,过表达UQCRC1可抑制结直肠癌细胞的增殖和迁移,是潜在的结直肠癌诊疗靶点。展开更多
Manganese(Mn),an essential trace element in the human body,plays critical roles in many biological processes.Recent studies have discovered that Mn^(2+)may promote or directly activate the cGAS-STING pathway,thereby s...Manganese(Mn),an essential trace element in the human body,plays critical roles in many biological processes.Recent studies have discovered that Mn^(2+)may promote or directly activate the cGAS-STING pathway,thereby subsequently initiating the natural immune response and augmenting antitumor therapy.However,the current lack of accurate methods for Mn^(2+)determination in cells significantly limits their mechanism investigation;hence,it is urgent to establish novel tools to detect Mn^(2+)in cells.In this study,the dual-emission carbon dots were initially synthesized via the one-pot hydrothermal method employing L-aspartic acid and p-phenylenediamine as raw materials.In the presence of Mn^(2+),the emission peak centered at 350 nm exhibited significant enhancement,whereas another peak at 610 nm remained stable.Consequently,a ratiometric sensor for Mn^(2+)determination was established using the signal at 350 nm as the responsive signal and the signal at 610 nm as an internal reference.Under the optimal condition,a good linear relationship was achieved between the F350/F610 value and Mn^(2+)concentration ranging from 0.9 to 15μmol/L,with a calculated LOD of 61 nmol/L.Benefiting from the special Mn^(2+)-induced ratiometric approach,this method demonstrates outstanding sensitivity,selectivity,and stability,rendering it applicable for Mn^(2+)determination in complex biological samples,as well as Mn^(2+)imaging in MKN-45 and LO2 cells.展开更多
目的探讨TLDC2在结直肠腺癌中的表达及意义。方法利用人类蛋白图谱(human protein atlas,HPA)和癌症基因组图谱(the cancer genome atlas,TCGA)数据库分析TLDC2蛋白和mRNA在结直肠腺癌中的表达。收集400例结直肠腺癌和447例其他类型实...目的探讨TLDC2在结直肠腺癌中的表达及意义。方法利用人类蛋白图谱(human protein atlas,HPA)和癌症基因组图谱(the cancer genome atlas,TCGA)数据库分析TLDC2蛋白和mRNA在结直肠腺癌中的表达。收集400例结直肠腺癌和447例其他类型实体瘤石蜡包埋组织制作组织芯片,应用免疫组化EnVision两步法检测TLDC2和SATB2蛋白表达情况。结果结直肠腺癌中TLDC2的阳性率显著高于SATB2(96.5%vs 87.0%),差异有统计学意义(P﹤0.0001),且低级别和高级别结直肠腺癌中TLDC2的阳性率均高于SATB2(99.4%vs 88.7%,P﹤0.0001;83.3%vs 79.2%,P=0.6699)。此外,在447例其他类型实体瘤中,TLDC2在神经内分泌肿瘤及胃、阑尾腺癌中有一定表达;SATB2则表达于少数黑色素瘤、卵巢癌、乳腺癌和胆囊癌。TLDC2在结直肠腺癌中的敏感性和特异性分别为97%(95%CI=0.94~0.98)、85%(95%CI=0.81~0.88),TLDC2和SATB2联合检测的敏感性和特异性分别为96%(95%CI=0.93~0.97)、93%(95%CI=0.90~0.95)。结论TLDC2是结直肠腺癌高度特异性和敏感的新标志物。展开更多
文摘双硫死亡状态与肿瘤患者炎症反应、免疫抑制和药物敏感性相关。然而,其在结直肠癌诊疗中的价值尚不清楚。基于此,研究使用单细胞测序数据和细胞特异性标记基因分析双硫死亡与不同结直肠癌细胞类型的相关性,发现结直肠癌高双硫死亡区域集中于上皮类细胞中。结合程序性细胞死亡蛋白1抑制剂治疗结直肠癌患者的肿瘤组织差异基因表达数据,建立双硫死亡相关预后模型分析发现,高双硫死亡水平结直肠癌患者风险较低,免疫治疗敏感性高。结合空间转录物组学分析发现,双硫死亡相关基因泛醇细胞色素C还原酶核心蛋白Ⅰ(ubiquinol-cytochrome c reductase core protein 1,UQCRC1)是潜在的结直肠癌诊疗靶点,其表达在上皮类结直肠癌细胞中较高,与结直肠癌免疫浸润区域存在共定位。进一步的生信分析和实验检测显示,UQCRC1在结直肠癌组织中低表达,过表达UQCRC1可抑制结直肠癌细胞的增殖和迁移,是潜在的结直肠癌诊疗靶点。
基金Supported by National Natural Science Foundation of China(22264023)Natural Science Foundation of Shaanxi Province(2024JC-YBQN-0150)+2 种基金Yan'an Science and Technology Bureau Project(2023-SFGG-057)Scientific Research Projects of Education Department of Shaanxi Province(22JK0614)PhD Start Fund of Yan'an University(YDBK2022-15)。
文摘Manganese(Mn),an essential trace element in the human body,plays critical roles in many biological processes.Recent studies have discovered that Mn^(2+)may promote or directly activate the cGAS-STING pathway,thereby subsequently initiating the natural immune response and augmenting antitumor therapy.However,the current lack of accurate methods for Mn^(2+)determination in cells significantly limits their mechanism investigation;hence,it is urgent to establish novel tools to detect Mn^(2+)in cells.In this study,the dual-emission carbon dots were initially synthesized via the one-pot hydrothermal method employing L-aspartic acid and p-phenylenediamine as raw materials.In the presence of Mn^(2+),the emission peak centered at 350 nm exhibited significant enhancement,whereas another peak at 610 nm remained stable.Consequently,a ratiometric sensor for Mn^(2+)determination was established using the signal at 350 nm as the responsive signal and the signal at 610 nm as an internal reference.Under the optimal condition,a good linear relationship was achieved between the F350/F610 value and Mn^(2+)concentration ranging from 0.9 to 15μmol/L,with a calculated LOD of 61 nmol/L.Benefiting from the special Mn^(2+)-induced ratiometric approach,this method demonstrates outstanding sensitivity,selectivity,and stability,rendering it applicable for Mn^(2+)determination in complex biological samples,as well as Mn^(2+)imaging in MKN-45 and LO2 cells.
文摘目的探讨TLDC2在结直肠腺癌中的表达及意义。方法利用人类蛋白图谱(human protein atlas,HPA)和癌症基因组图谱(the cancer genome atlas,TCGA)数据库分析TLDC2蛋白和mRNA在结直肠腺癌中的表达。收集400例结直肠腺癌和447例其他类型实体瘤石蜡包埋组织制作组织芯片,应用免疫组化EnVision两步法检测TLDC2和SATB2蛋白表达情况。结果结直肠腺癌中TLDC2的阳性率显著高于SATB2(96.5%vs 87.0%),差异有统计学意义(P﹤0.0001),且低级别和高级别结直肠腺癌中TLDC2的阳性率均高于SATB2(99.4%vs 88.7%,P﹤0.0001;83.3%vs 79.2%,P=0.6699)。此外,在447例其他类型实体瘤中,TLDC2在神经内分泌肿瘤及胃、阑尾腺癌中有一定表达;SATB2则表达于少数黑色素瘤、卵巢癌、乳腺癌和胆囊癌。TLDC2在结直肠腺癌中的敏感性和特异性分别为97%(95%CI=0.94~0.98)、85%(95%CI=0.81~0.88),TLDC2和SATB2联合检测的敏感性和特异性分别为96%(95%CI=0.93~0.97)、93%(95%CI=0.90~0.95)。结论TLDC2是结直肠腺癌高度特异性和敏感的新标志物。
