血小板计数、癌胚抗原和蛋白基因产物9.5对晚期非小细胞肺癌患者疗效和预后的价值

Value of platelet count,carcinoembryonic antigen and protein gene product 9.5 on the outcome and prognosis of advanced non-small cell lung cancer

目的探究血小板计数(PLT)、癌胚抗原(CEA)和蛋白基因产物9.5(PGP9.5)水平对晚期非小细胞肺癌(NSCLC)患者疗效和预后的预测价值。方法本研究为回顾性队列研究。采用非随机抽样的方法纳入2016年1月至2022年12月在空军军医大学唐都医院确诊并接受紫杉类+顺铂化疗方案治疗的62例晚期NSCLC患者。采用电话和门诊随访的方式对患者的预后情况进行追踪调查,随访时间至少半年,随访截止日期为2023年6月。评估所有患者化疗后6个月的疗效,根据实体瘤疗效评价标准将所有患者分为进展组(疾病进展,37例)和缓解组(完全缓解+部分缓解+疾病稳定,25例)。收集患者的一般资料(性别、年龄、吸烟史、手术史、临床分期和病理类型),化疗前1周PLT、肿瘤标志物[鳞状细胞癌相关抗原(SCC)、铁蛋白(FRT)、细胞角蛋白19片段(CYFRA21-1)、CEA、肿瘤标志物糖类抗原50(CA50)、神经元特异性烯醇化酶(NSE)、糖类抗原125(CA125)]水平和肺癌自身抗体(抑癌基因53(P53)、PGP9.5、肿瘤/睾丸抗原G抗原7(GAGE7)、三磷酸腺苷结合RNA解旋酶自身抗体4-5(GBU4-5)、性别决定基因家族2(SOX2)、黑色素瘤抗原A1(MAGEA1)、肿瘤相关基因(CAGE))水平。比较2组患者一般资料,化疗前PLT、肿瘤标志物和肺癌自身抗体的水平。采用受试者操作特征(ROC)曲线分析化疗前PLT、肿瘤标志物和肺癌自身抗体对晚期NSCLC患者疗效的预测效能。采用多因素logistic回归分析确定影响晚期NSCLC患者疗效的独立危险因素。采用Kaplan-Meier法绘制生存曲线,Log-rank检验比较不同表达水平的各独立危险因素患者的生存状态。结果缓解组中男17例,女8例,年龄62.0(53.0,69.0)岁;进展组中男27例,女10例,年龄63.0(56.0,69.0)岁。2组患者的临床分期比较差异有统计学意义(χ^(2)=1.98,P=0.048);性别、年龄、吸烟史、手术史和病理类型比较,差异均无统计学意义(均P>0.05)。进展组患者化疗前PLT、CEA、CA125、PGP9.5、GBU4-5和CAGE的表达水平均高于缓解组,差异均有统计学意义(均P<0.05)。2组患者化疗前FRT、NSE、CYFRA21-1、CA50、SCC、P53、SOX2、GAGE7和MAGEA1水平比较,差异均无统计学意义(均P>0.05)。ROC曲线分析显示,PLT、CEA、CA125、PGP9.5、GBU4-5和CAGE预测NSCLC患者疗效的曲线下面积分别为0.756(95%CI:0.614~0.874)、0.854(95%CI:0.746~0.947)、0.760(95%CI:0.633~0.887)、0.788(95%CI:0.664~0.912)、0.739(95%CI:0.604~0.875)和0.741(95%CI:0.608~0.875),最佳截断值分别为221.00×10^(9)/L、5.00 U/L、35.00 U/L、3.08 U/ml、9.91 U/ml和0.37 U/ml,预测效能良好。多因素logistic回归分析显示,PLT>221.00×10^(9)/L、CEA>5.00 U/L和PGP9.5>3.08 U/ml是影响晚期NSCLC患者疗效的独立危险因素(OR值分别为1.015、1.191、1.906,均P<0.05)。所有患者总体的中位生存时间为12.22个月(95%CI:9.02~15.43)。PLT高表达(>221.00×10^(9)/L)患者的中位生存时间为22.00个月(95%CI:18.65~25.35),PLT低表达(≤221.00×10^(9)/L)的中位生存时间为27.00个月(95%CI:19.28~34.73),化疗前PLT低表达患者的生存状态优于PLT高表达患者(χ^(2)=9.00,P=0.003)。CEA高表达(>5.00 U/L)患者的中位生存时间为18.80个月(95%CI:13.12~22.89),CEA低表达(≤5.00 U/L)的中位生存时间为27.30个月(95%CI:24.31~29.69),化疗前CEA低表达患者的生存状态优于CEA高表达患者(χ^(2)=7.29,P=0.016)。PGP9.5高表达(>3.08 U/ml)患者的中位生存时间为7.76个月(95%CI:4.76~9.24),PGP9.5低表达(≤3.08 U/ml)的中位生存时间为25.31个月(95%CI:22.81~27.16),化疗前PGP9.5低表达患者的生存状态优于PGP9.5高表达患者(χ^(2)=21.66,P<0.001)。结论PLT、CEA和PGP9.5的表达水平可用于晚期NSCLC患者化疗疗效预测和预后评估。

Objective To investigate the effects of platelet count(PLT),carcinoembryonic antigen(CEA)and protein gene product 9.5(PGP9.5)levels on the efficacy and prognosis of advanced non-small cell lung cancer(NSCLC).Methods This study was a retrospective cohort study.Sixty-two patients with advanced NSCLC diagnosed and treated with paclitaxel+cisplatin chemotherapy regimen in Tangdu Hospital,Air Force Medical University from January 2016 to December 2022 were included using non-random sampling.The prognosis was followed up by telephone contact and outpatient examinations for at least six months until June 2023.The efficacy at 6 months of chemotherapy was evaluated,and all patients were divided into the progression group(disease progression,37 cases)and the remission group(complete and/or partial remission plus stable disease,25 cases)according to the criteria for evaluating the efficacy of solid tumors.General information(gender,age,smoking history,surgical history,tumor stage and pathological staging),PLT,tumor markers(squamous cell carcinoma-associated antigen[SCC],ferritin[FRT],cytokeratin 19 fragment[CYFRA21-1],CEA,tumor markers glycan antigen 50[CA50],neuron-specific enolase[NSE],glycan antigen 125[CA125])levels and lung cancer autoantibodies(tumor suppressor gene 53[P53],PGP9.5,cancer/testis antigens[GAGE7],adenosine triphosphate-binding RNA deconjugase 4-5[GBU4-5],sex determining region Y-box 2[SOX2],MAGE family member A1[MAGEA1],cancer gene[CAGE])levels were recorded.General information,and PLT level,tumor markers and lung cancer autoantibodies before chemotherapy were compared between the two groups.The predictive efficacy of PLT level,tumor markers and lung cancer autoantibodies before chemotherapy on the outcome of advanced NSCLC was analyzed using the receiver operating characteristic(ROC)curves.Multivariate logistic regression analysis was used to determine the independent risk factors for the outcome of advanced NSCLC.Kaplan-Meier survival curves were plotted,followed by comparing the survival in patients carrying opposite risk factors by the log-rank tests.Results In the remission group,there were 17 males and 8 females aged 62.0(53.0,69.0)years.In the progression group,there were 27 males and 10 females aged 63.0(56.0,69.0)years.There was a significant difference in the clinical staging of advanced NSCLC between the remission group and progression group(χ^(2)=1.98,P=0.048).No significant differences in gender,age,smoking history,surgical history,and pathological type were detected between groups(all P>0.05).The expression levels of PLT,CEA,CA125,PGP9.5,GBU4-5 and CAGE before chemotherapy were significantly higher in the progression group than those of remission group(all P<0.05).There were no significant differences in the FRT,NSE,CYFRA21-1,CA50,SCC,P53,SOX2,GAGE7 and MAGEA1 before chemotherapy between the two groups(all P>0.05).ROC curve analysis showed that the area under the curve(AUC)of PLT,CEA,CA125,PGP9.5,GBU4-5 and CAGE for predicting the efficacy of chemotherapy on advanced NSCLC was 0.756(95%CI:0.614-0.874),0.854(95%CI:0.746-0.947),0.760(95%CI:0.633-0.887),0.788(95%CI:0.664-0.912),0.739(95%CI:0.604-0.875),and 0.741(95%CI:0.608-0.875),respectively.The corresponding optimal cut-off values of PLT,CEA,CA125,PGP9.5,GBU4-5 and CAGE were 221.00×10^(9)/L,5.00 U/L,35.00 U/L,3.08 U/ml,9.91 U/ml and 0.37 U/ml,respectively,with a good predictive efficacy.Multivariate logistic regression analysis showed that PLT>221.00×10^(9)/L,CEA>5.00 U/L and PGP9.5>3.08 U/ml were independent risk factors for the outcome of advanced NSCLC(odds ratio=1.015,1.191,and 1.906,respectively;all P<0.05).The overall median survival time of the total cohort was 12.22 months(95%CI:9.02-15.43),which,in advanced NSCLC patients expressing high(>221.00×10^(9)/L)and low PLT levels(≤221.00×10^(9)/L)was 22.00 months(95%CI:18.65-25.35)and 27 months(95%CI:19.28-34.73),respectively.The survival status of advanced NSCLC patients with low PLT levels before chemotherapy was superior than those expressing high PLT levels(χ^(2)=9.00,P=0.003).The median survival time of advanced NSCLC patients carrying high(>5.00 U/L)and low CEA levels(≤5.00 U/L)was 18.80 months(95%CI:13.12-22.89)and 27.30 months(95%CI:24.31-29.69),respectively.The survival status of patients with low CEA levels before chemotherapy was superior than those with high CEA levels(χ^(2)=7.29,P=0.016).The median survival time of patients with high(>3.08 U/ml)and low PGP9.5 levels(≤3.08 U/ml)was 7.76 months(95%CI:4.76-9.24)and 25.31 months(95%CI:22.81-27.16),respectively.The survival status of advanced NSCLC patients with low PGP9.5 levels before chemotherapy was superior than those with high PGP9.5 levels(χ^(2)=21.66,P<0.001).Conclusions Expression levels of PLT,CEA and PGP9.5 before chemotherapy can be used to predict the efficacy of paclitaxel+cisplatin chemotherapy regimen and prognosis of advanced NSCLC patients.