异常糖链糖蛋白、热休克蛋白90α及双皮质素样激酶1表达与非小细胞肺癌患者临床分期的关系

Relationship between expression of abnormal glycophoprotein,heat shock protein 90αand double cortin-like kinase 1 and clinical stage in patients with non-small cell lung cancer

目的探讨异常糖链糖蛋白(TAP)、热休克蛋白90α(HSP90α)及双皮质素样激酶1(DCLK1)表达与非小细胞肺癌(NSCLC)患者临床分期的关系。方法本研究为病例对照研究,选取2020年1月至2022年1月山西省肿瘤医院呼吸科收治的72例NSCLC住院患者作为NSCLC组,男50例,女22例,年龄(64.13±10.23)岁,年龄范围为51~78岁,同时选取同期住院经临床、影像学、病理检查等排除恶性肿瘤的肺良性疾病患者50例作为良性组,男34例,女16例,年龄(65.09±10.05)岁,年龄范围为48~79岁。分别检测两组患者化学治疗前及化学治疗后NSCLC组患者的TAP、HSP90α及DCLK1的表达水平;采用受试者操作特征(ROC)曲线分析TAP、HSP90α、DCLK1单项指标及联合指标对NSCLC患者的诊断效能;采用多元线性回归分析对TAP、HSP90α及DCLK1与肿瘤临床分期和化学治疗效果进行相关性分析;对影像学治疗效果进行评估。结果治疗前,NSCLC组患者TAP[(196.20±20.13)μm^(2)]、HSP90α[(66.35±10.13)μg/L]及DCLK1[(6.54±2.01)μg/L]的表达水平均高于良性组[(137.23±10.36)μm^(2)、(50.22±8.24)μg/L、(2.82±1.37)μg/L],差异有统计学意义(P<0.05)。化学治疗后,NSCLC组患者TAP[(154.23±10.24)μm^(2)、HSP90α[(55.17±8.09)μg/L]及DCLK1[(3.67±1.42)μg/L]的表达水平均低于化学治疗前,差异有统计学意义(P<0.05)。TAP、HSP90α、DCLK1联合诊断的灵敏度、特异度和准确度分别为100%、98.0%和99.2%,高于各指标单独诊断,差异有统计学意义(P<0.05)。ROC曲线分析显示TAP、HSP90α、DCLK1各指标单独及联合诊断NSCLC的曲线下面积分别为0.998(95%CI:0.993~1.000)、0.889(95%CI:0.833~0.944)、0.916(95%CI:0.868~0.964)、0.999(95%CI:0.997~1.000),差异有统计学意义(P<0.05)。NSCLC患者Ⅲ期、Ⅳ期TAP、HSP90α及DCLK1水平比较,差异有统计学意义(P<0.05)。TAP、HSP90α与肿瘤临床分期均存在相关性(P<0.05)。多元线性回归模型结果显示,TAP、HSP90α、DCLK1水平与化学治疗效果均存在相关性(P<0.05)。治疗4个周期后,NSCLC组患者完全缓解13例,部分缓解30例,缓解率为59.7%(43/72)。结论NSCLC患者的TAP、HSP90α及DCLK1表达水平经治疗后会降低,3指标联合检测的灵敏度、特异度及准确性高于各指标单独检测,NSCLC患者TAP、HSP90α及DCLK1的水平与临床分期存在一定的关系,TAP、HSP90α、DCLK1水平与化学治疗效果均存在相关性,化学治疗后NSCLC患者的缓解率较高。

Objective To explore the relationship between the clinical stage of tumor abnormal protein(TAP),heat shock protein 90α(HSP90α)and double cortin-like kinase 1(DCLK1)expression in non-small cell lung cancer(NSCLC)patients.Methods This study was a case control study,from January 2020 to January 2022,a total of 72 NSCLC inpatients admitted to the Respiratory Department of Shanxi Cancer Hospital were selected as the NSCLC group,50 males and 22 females,aged(64.13±10.23)years old,ranging from 51 to 78 years old.At the same time,a total of 50 patients with benign pulmonary diseases excluded from malignant tumors by clinical,imaging and pathological examinations were selected as the benign group,34 males and 16 females,aged(65.09±10.05)years old,ranging from 48 to 79 years old.The expression levels of TAP,HSP90αand DCLK 1 were measured in the NSCLC group before and after chemotherapy in both groups.TAP and HSP90αwere analyzed by receiver operator characteristic(ROC)curve,diagnostic efficacy of DCLK1 single index and combined index in patients with NSCLC,use multiple linear regression analysis to analyze TAP and HSP90α.The correlation between DCLK1 and clinical stage and chemotherapy effect was analyzed,to evaluate the effect of imaging treatment.Results Before the treatment,the expression levels of TAP[(196.20±20.13)μm^(2)],HSP90α[(66.35±10.13)μg/L],and DCLK1[(6.54±2.01)μg/L]in the NSCLC group were higher than those in the benign group[(137.23±10.36)μm^(2),(50.22±8.24)μg/L,(2.82±1.37)μg/L],the differences were statistically significant(P<0.05).After the chemotherapy,the expression levels of TAP[(154.23±10.24)μm^(2),HSP90α[(55.17±8.09)μg/L]and DCLK 1[(3.67±1.42)μg/L]in NSCLC patients were lower than those observed before chemotherapy,the differences were statistically significant(P<0.05).The sensitivity,specificity,and accuracy of the combined TAP,HSP90α,and DCLK1 were 100%,98.0%,and 99.2%respectively,which were higher than each index alone,the difference was statistically significant(P<0.05).ROC curve analysis showed that the area under the curve of TAP,HSP90α,and DCLK 1 were 0.998(95%CI:0.993 to 1.000),0.889(95%CI:0.833 to 0.944),0.916(95%CI:0.868 to 0.964),and 0.999(95%CI:0.997 to 1.000)respectively,the difference was statistically significant(P<0.05).Comparison of tumor staging stageⅢ,ⅣTAP,HSP90αand DCLK 1 levels in NSCLC,the difference was statistically significant(P<0.05).There were correlation among TAP,HSP90αand tumor clinical stage(P<0.05).The results of the multiple linear regression model showed that the TAP,HSP90αand DCLK 1 levels and the effect of chemotherapy treatment were all correlated(P<0.05).After 4 cycles of treatment,13 patients in the NSCLC group had complete response and 30 partial responses,with a response rate of 59.7%(43/72).Conclusions TAP,HSP90αand DCLK 1 expression levels in NSCLC patients will decrease after treatment.The sensitivity,specificity and accuracy of the combined detection of the three indexes are higher than that of each index alone,and the levels of TAP,HSP90αand DCLK1 and the clinical stage,and the levels of TAP,HSP90αand DCLK1 and the chemotherapy effect are related,better remission rate in NSCLC patients after chemotherapy.