慢性肺源性心脏病患者血清GSK⁃3β、β⁃catenin mRNA表达水平与病情严重程度及预后的关系

Relationship between serum GSK⁃3βandβ⁃catenin mRNA expression levels and disease severity and prognosis in pa⁃tients with chronic pulmonary heart disease

目的分析慢性肺源性心脏病(CPHD)患者血清中糖原合成酶激酶⁃3β(GSK⁃3β)、β⁃连环蛋白(β⁃catenin)信使RNA(mRNA)表达水平与病情严重程度及预后的关系。方法选取2020年1月—2021年10月汉中市三二〇一医院收治的CPHD患者108例作为CPHD组,根据肺心功能分为失代偿亚组40例、代偿亚组68例,根据患者1年内生存情况分为存活亚组85例、死亡亚组23例。以同期健康体检者108例为健康对照组。收集CPHD患者的基本资料,荧光定量PCR法检测受试者血清GSK⁃3β、β⁃catenin mRNA表达水平;比较各组血清GSK⁃3β、β⁃catenin mRNA表达水平差异;Pearson法分析CPHD患者血清GSK⁃3β、β⁃catenin mRNA表达水平的相关性,多因素Cox回归分析影响CPHD患者死亡的危险因素,受试者工作特征曲线(ROC)分析血清GSK⁃3β、β⁃catenin mRNA表达水平对CPHD患者死亡的预测价值。结果与健康对照组比较,CPHD组血清GSK⁃3βmRNA表达水平显著降低,β⁃catenin mRNA表达水平显著升高(t/P=28.208/<0.001、25.981/<0.001);与代偿亚组比较,失代偿亚组血清GSK⁃3βmRNA表达水平显著降低,β⁃catenin mRNA表达水平显著升高(t/P=12.572/<0.001、12.156/<0.001);与存活亚组比较,死亡亚组吸烟史比例、PaCO_(2)、β⁃catenin mRNA表达水平显著升高,PaO_(2)、GSK⁃3βmRNA表达水平显著降低[χ^(2)(t)/P=5.941/0.015、3.690/<0.001、7.353/<0.001、2.723/0.008、5.730/<0.001];CPHD患者血清GSK⁃3βmRNA与β⁃catenin mRNA表达水平呈负相关(r/P=-0.502/<0.001);GSK⁃3βmRNA高表达是CPHD患者死亡的保护因素[HR(95%CI)=0.843(0.728~0.976)],β⁃catenin mRNA高表达是其危险因素[HR(95%CI)=1.391(1.041~1.859)];血清GSK⁃3β、β⁃catenin mRNA及二者联合预测CPHD患者死亡的曲线下面积分别为0.838、0.884、0.913,均有较好的预测价值。结论CPHD患者血清GSK⁃3βmRNA呈低表达,β⁃catenin mRNA呈高表达,二者与病情严重程度及预后相关,且对患者预后有较高预测效能。

Objective To analyze the relationship between serum glycogen synthase kinase⁃3β(GSK⁃3β)andβ⁃catenin messenger RNA(mRNA)expression levels and disease severity and prognosis in patients with chronic pulmonary heart disease(CPHD).Methods One hundred and eight patients with CPHD admitted to the 321 Hospital of Hanzhong Cit⁃y from January 2020 to October 2021 were selected as the CPHD group.They were divided into a decompensated subgroup of 40 cases and a compensated subgroup of 68 cases based on pulmonary and cardiac function.They were divided into a sur⁃vival subgroup of 85 cases and a death subgroup of 23 cases based on their one⁃year survival.A healthy control group consis⁃ted of 108 healthy individuals who underwent physical examinations during the same period.Collect basic data of CPHD pa⁃tients and detect serum GSK⁃3βin subjects using fluorescence quantitative PCR method.Compare the expression level ofβ⁃catenin mRNA,serum GSK⁃3βlevels in each group,Differences in expression levels ofβ⁃catenin mRNA;Pearson method for analyzing correlation ofβ⁃catenin mRNA expression levels and serum GSK⁃3βin patients with CPHD,multivariate Cox re⁃gression analysis of risk factors for death in CPHD patients,and analysis of serum GSK⁃3βusing receiver operating character⁃istic curve(ROC),The predictive value ofβ⁃catenin mRNA expression levels for mortality in patients with CPHD.Results Compared with the healthy control group,the serum mRNA expression level of GSK⁃3βin the CPHD group was significant⁃ly reduced,the expression level ofβ⁃catenin mRNA was significantly increased(t/P=28.208/<0.001,25.981/<0.001).Com⁃pared with the compensatory subgroup,the serum mRNA expression level of GSK⁃3βin the decompensated subgroup was significantly reduced,The expression level ofβ⁃catenin mRNA was significantly increased(t/P=12.572/<0.001,12.156/<0.001).Compared with the survival subgroup,the proportion of smoking history,PaCO_(2)and the expression level ofβ⁃catenin mRNA significantly increased,with PaO_(2) and GSK⁃3βSignificantly reduced mRNA expression levels[χ^(2)(t)/P=5.941/0.015,3.690/<0.001,7.353/<0.001,2.723/0.008,5.730/<0.001].Serum GSK⁃3βfrom patients with CPHD MRNA and the expression level ofβ⁃catenin mRNA was negatively correlated(r/P=-0.502/<0.001).GSK⁃3βHigh mRNA expression is a protective factor for death in patients with CPHD[HR(95%CI)=0.843(0.728-0.976)],High expression ofβ⁃catenin mR⁃NA is a risk factor[HR(95%CI)=1.391(1.041-1.859)].Serum GSK⁃3β,the area under the curve ofβ⁃catenin mRNA and their combination in predicting death in CPHD patients is 0.838,0.884,and 0.913,respectively,both of which have good predictive value.Conclusion Serum GSK⁃3βfrom patients with CPHD MRNA expression is low,β⁃catenin mRNA is high⁃ly expressed,which is related to the severity of the condition and prognosis,and has a high predictive power for patient prog⁃nosis.