Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is asso...Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.展开更多
目的探讨术前中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)对直肠癌根治术后手术部位感染(SSI)的预测价值。方法回顾性分析2015年1月-2018年8月解放军总医院第一医学中心普通外科连续收治的298例直肠癌根治术患者,根据术后...目的探讨术前中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)对直肠癌根治术后手术部位感染(SSI)的预测价值。方法回顾性分析2015年1月-2018年8月解放军总医院第一医学中心普通外科连续收治的298例直肠癌根治术患者,根据术后30d是否发生SSI分为SSI组(n=20)和对照组(n=278)。比较两组患者的性别、年龄、是否行术前新辅助放化疗、手术方式、肿瘤T分期情况及术前的中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平。SSI组患者根据开腹与微创手术进行亚组分析,比较两个亚组患者的性别、年龄、是否行术前新辅助放化疗、肿瘤T分期情况及术前的中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平。应用ROC曲线分析术前NLR、PLR对直肠癌根治术后SSI的预测价值。结果 SSI组男女比例高于对照组(19/1 vs. 178/100),差异有统计学意义(P=0.005)。两组年龄、非恢复性手术比例、微创手术比例、新辅助治疗比例、肿瘤T分期、术前白蛋白及血红蛋白水平等差异均无统计学意义(P>0.05)。两组术前中性粒细胞计数[(3.96±1.03)×10~9/L vs.(3.62±1.28)×10~9/L,P=0.245]、淋巴细胞计数[(1.47±0.45)×10~9/L vs.(1.71±0.64)×10~9/L,P=0.103]、血小板计数[(249.10±57.42)×10~9/Lvs.(230.21±68.53)×10~9/L,P=0.231]差异均无统计学意义。SSI组术前NLR高于对照组(2.77±0.52 vs. 2.39±1.23),差异有统计学意义(P=0.010),而PLR与对照组比较差异无统计学意义(184.46±69.54vs.152.93±73.82,P=0.065)。SSI组内开腹手术亚组患者年龄明显低于微创手术亚组,差异有统计学意义(P=0.018),两亚组性别、非恢复性手术比例、新辅助治疗比例、肿瘤T分期、术前中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平比较差异均无统计学意义(P>0.05)。术前NLR预测直肠癌根治术后SSI的AUC为0.711(95%CI 0.643～0.779),最佳临界值为2.13,灵敏度为95.0%,特异度为51.4%。术前PLR预测直肠癌根治术后SSI的AUC为0.665(95%CI 0.553～0.777),最佳临界值为150.69,灵敏度为75.0%,特异度为59.7%。结论术前NLR和PLR对直肠癌根治术后SSI的发生有一定预测价值。展开更多
文摘Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.
文摘目的探讨术前中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)对直肠癌根治术后手术部位感染(SSI)的预测价值。方法回顾性分析2015年1月-2018年8月解放军总医院第一医学中心普通外科连续收治的298例直肠癌根治术患者,根据术后30d是否发生SSI分为SSI组(n=20)和对照组(n=278)。比较两组患者的性别、年龄、是否行术前新辅助放化疗、手术方式、肿瘤T分期情况及术前的中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平。SSI组患者根据开腹与微创手术进行亚组分析,比较两个亚组患者的性别、年龄、是否行术前新辅助放化疗、肿瘤T分期情况及术前的中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平。应用ROC曲线分析术前NLR、PLR对直肠癌根治术后SSI的预测价值。结果 SSI组男女比例高于对照组(19/1 vs. 178/100),差异有统计学意义(P=0.005)。两组年龄、非恢复性手术比例、微创手术比例、新辅助治疗比例、肿瘤T分期、术前白蛋白及血红蛋白水平等差异均无统计学意义(P>0.05)。两组术前中性粒细胞计数[(3.96±1.03)×10~9/L vs.(3.62±1.28)×10~9/L,P=0.245]、淋巴细胞计数[(1.47±0.45)×10~9/L vs.(1.71±0.64)×10~9/L,P=0.103]、血小板计数[(249.10±57.42)×10~9/Lvs.(230.21±68.53)×10~9/L,P=0.231]差异均无统计学意义。SSI组术前NLR高于对照组(2.77±0.52 vs. 2.39±1.23),差异有统计学意义(P=0.010),而PLR与对照组比较差异无统计学意义(184.46±69.54vs.152.93±73.82,P=0.065)。SSI组内开腹手术亚组患者年龄明显低于微创手术亚组,差异有统计学意义(P=0.018),两亚组性别、非恢复性手术比例、新辅助治疗比例、肿瘤T分期、术前中性粒细胞计数、淋巴细胞计数、血小板计数、NLR、PLR、白蛋白和血红蛋白水平比较差异均无统计学意义(P>0.05)。术前NLR预测直肠癌根治术后SSI的AUC为0.711(95%CI 0.643～0.779),最佳临界值为2.13,灵敏度为95.0%,特异度为51.4%。术前PLR预测直肠癌根治术后SSI的AUC为0.665(95%CI 0.553～0.777),最佳临界值为150.69,灵敏度为75.0%,特异度为59.7%。结论术前NLR和PLR对直肠癌根治术后SSI的发生有一定预测价值。
