血清标志物在乳腺癌骨转移诊断中的临床价值

Value of serum markers in the diagnosis of bone metastasis of breast cancer

目的探讨白蛋白与碱性磷酸酶比值(AAPR)、血清碱性磷酸酶(ALP)、ALP/红细胞分布宽度(RDW)、中性粒细胞与淋巴细胞比率(NLR)和糖类抗原15-3(CA15-3)在乳腺癌骨转移发生前后的差异及在临床诊断中的价值。方法回顾性分析2016-01-01-2018-07-31中国医学科学院肿瘤医院收治的156例乳腺癌初诊患者临床资料,其中包括无骨转移组130例、骨转移组26例;采用简单随机抽样法选取同期54名健康体检者作为健康对照组;比较3组的AAPR、ALP、ALP/RDW、NLR和CA15-3水平。同时采用受试者工作特征曲线(ROC)分析各项指标单独及联合检测对乳腺癌骨转移的诊断效能。无骨转移组在随访过程中34例患者发生骨转移,比较其骨转移前后5项指标水平。结果乳腺癌骨转移组、无骨转移组和健康对照组的AAPR分别为0.47(0.38,0.64)、0.72(0.59,0.91)和0.75(0.64,0.93),H=23.076,P<0.001;ALP分别为89.00(70.25,120.18)、61.50(50.75,77.25)和60.50(48.75,74.25),H=18.913,P<0.001;ALP/RDW分别为6.65(5.57,9.41)、4.76(3.79,6.01)和4.56(3.87,5.80),H=19.343,P<0.001;NLR分别为2.79(1.64,3.85)、2.05(1.46,2.92)和1.82(1.36,2.21),H=12.239,P=0.002;CA15-3分别为24.04(14.50,124.80)、10.07(7.66,15.45)和7.08(5.82,10.67),H=53.486,P<0.001。本研究所有纳入者的AAPR、ALP、ALP/RDW、NLR和CA15-3分别用于诊断乳腺癌骨转移时,ROC曲线下面积(AUC)分别为0.786、0.761、0.763、0.679和0.884,将上述5项指标联合用于诊断时,AUC为0.914,灵敏度为0.962,特异度为0.743。动态检测无骨转移组患者治疗过程中的5项指标发现,发生骨转移时ALP(93.57±53.95)、ALP/RDW(7.06±3.73)、NLR(2.41±0.97)和CA15-3(58.94±71.12)的水平较骨转移前均升高,差异有统计学意义,t值分别为3.17、3.19、2.31和3.71,P值分别为0.004、0.003、0.028和0.001;而AAPR在骨转移后(0.59±0.24)水平较骨转移前(0.73±0.23)降低,差异有统计学意义,t=-3.79,P=0.001。结论AAPR、ALP、ALP/RDW、NLR和CA15-3对乳腺癌骨转移有较高的诊断价值,联合检测可提高诊断效能。

Objective To compare the differences of serum albumin-to-alkaline phosphatase ratio(AAPR),alkaline phosphatase(ALP),ALP/red cell distribution width(RDW),NLR and CA15-3 in breast cancer before and after bone metastasis and to explore the clinical values in the diagnosis of bone metastasis of breast cancer patients.Methods Retrospective analysis was performed on the clinical data of 156 newly diagnosed breast cancer patients who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences between January 1,2016 and July 31,2018.Patients were divided into two groups:those with bone metastases(n=26)and those without(n=130).A control group of 54 healthy people was enrolled throughout the same time period using simple random sampling method.The levels of AAPR,ALP,ALP/RDW,NLR and CA15-3among three groups were compared.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of individual and combined detection of five markers for breast cancer bone metastases.During the follow-up period,34patients in the non-bone metastasis breast cancer group developed bone metastases,the five indicators of 34patients were analyzed before and after bone metastases.Results The AAPR of bone metastasis group of breast cancer,non bone metastasis group and healthy control group were 0.47(0.38,0.64),0.72(0.59,0.91),0.75(0.64,0.93),respectively,H=23.076,P<0.001;The ALP of the three groups were 89.00(70.25,120.18),61.50(50.75,77.25),60.50(48.75,74.25),respectively,H=18.913,P<0.001;The ALP/RDW of the there groups were 6.65(5.57,9.41),4.76(3.79,6.01),4.56(3.87,5.80),respectively,H=19.343,P<0.001;The NLR of the there groups were 2.79(1.64,3.85),2.05(1.46,2.92),1.82(1.36,2.21),respectively,H=12.239,P=0.002;The CA15-3of the there groups were 24.04(14.50,124.80),10.07(7.66,15.45),7.08(5.82,10.67),respectively,H=53.486,P<0.001.When AAPR,ALP,ALP/RDW,NLR and CA15-3of all participants were used to diagnose bone metastases of breast cancer,the area under ROC curve(AUC)were 0.786,0.761,0.763,0.679and 0.884,respectively.When five indicators were detected simultaneously,the specificity was 0.743,the sensitivity was 0.962,and the AUC was 0.914.In the patient group without bone metastasis,dynamic detection of five indicators during treatment revealed statistically significant increased in ALP(93.57±53.95),ALP/RDW(7.06±3.73),NLR(2.41±0.97),and CA15-3(58.94±71.12)levels when compared to pre-metastasis,the t values were 3.17,3.19,2.31and 3.71,and the Pvalues were 0.004,0.003,0.028and 0.001,respectively.Affer bone metastasis,the level of AAPR(0.59±0.24)significantly decreased compared to before(0.73±0.23),t=-3.79,P=0.001.Conlusions The diagnostic value of AAPR,ALP,ALP/RDW,NLR and CA15-3for breast cancer bone metastases is significant,and the diagnostic effectiveness of combination detection can be increased.