中华检验医学杂志
中華檢驗醫學雜誌
중화검험의학잡지
CHINESE JOURNAL OF LABORATORY MEDICINE
2013年
8期
708-712
,共5页
荆结线%杜丽莉%徐晓琴%田保国%孙婷%赵先文%韩存芝
荊結線%杜麗莉%徐曉琴%田保國%孫婷%趙先文%韓存芝
형결선%두려리%서효금%전보국%손정%조선문%한존지
癌,小细胞%肺肿瘤%肽碎片%重组蛋白质类%治疗结果%预后
癌,小細胞%肺腫瘤%肽碎片%重組蛋白質類%治療結果%預後
암,소세포%폐종류%태쇄편%중조단백질류%치료결과%예후
Carcinoma,small cell%Lung neoplasms%Peptide fragments%Recombinant proteins%Treatment outcome%Prognosis
目的 探讨血清胃泌素前体释放肽(ProGRP)对小细胞肺癌(SCLC)疗效监测的临床意义,评估ProGRP水平与SCLC预后的关系.方法 临床诊断研究.用ELISA检测2005年12月至2008年10月期间山西省肿瘤医院呼吸与放疗科治疗、有完整资料的SCLC患者413例,非小细胞肺癌(NSCLC)418例、良性疾病患者120例及200名健康人的血清ProGRP、NSE水平.2005年12月至2011年10月随访368例SCLC患者ProGRP水平.以413例SCLC患者标本绘制ProGRP、NSE受试者工作特征曲线(ROC)；Kaplan-Meier法分析SCLC患者生存时间,Cox比例风险模型分析影响SCLC患者预后的因素.结果 ProGRP诊断SCLC的ROC曲线AUC为0.798(95％ CI:0.746 ～0.850),以45.3 μg/L为临界值,其敏感度、特异度分别为79.2％,98.1％；NSE诊断SCLC的ROC曲线AUC为0.786 (95％ CI:0.726 ～0.746),以12.4 μg/L为临界值,其敏感度、特异度分别为71.9％,96.7％；ProGRP与NSE联合诊断SCLC的敏感度、特异度分别为88.1％,95.8％.SCLC患者治疗前血清ProGRP为1758.7(368.4 ～2967.3) μg/L,高于NSCLC患者组[21.3(18.6～35.2) μg/L]、肺良性疾病组[36.8(26.3 ～43.4) μg/L]和健康对照组[6.89(5.3～8.6) μg/L],差异有统计学意义(H=103.66,P=0.000).Ⅰ～Ⅱ期、Ⅲ期、Ⅳ期SCLC患者血清ProGRP分别为543.3(256.8 ～ 843.2)、1440.6(1042.4 ～ 2543.3)、1897.6(1586.5 ～3958.7) μg/L,差异有统计学意义(H=25.974,P=0.000).完全缓解(CR)的165例患者治疗后ProGRP水平[226.3(69.3 ～456.7) μg/L]比治疗前[1025.2(436.8 ～1060.9) μg/L]明显下降(U=11.65,P＜0.01)；部分缓解(PR)的146例患者治疗后ProGRP水平[563.7(246.2 ～869.4)μg/L]与治疗前[1351.5(859.5 ～1883.4) μg/L]相比有所下降(U =9.17,P＜0.01)；治疗后病情无变化(NR)的63例患者[1575.6(1025.8～2596.5)μg/L]与病情进展(PD)的39例患者[2418.7(1869.2 ～4362.3)μg/L]与治疗前ProGRP水平[分别为1280.2(863.4～ 1968.7)、1867.6 (1689.3 ～3025.4) μg/L]相比,则明显升高(U值分别为3.314、2.54,P均＜0.01).随访至少3年的SCLC患者368例,随访率为89.1％(368/413).119例治疗前ProGRP＜1000μg/L的SCLC患者死亡56例,中位生存时间为16(4 ～23)个月,249例治疗前ProGRP＞1000 μg/L SCLC患者死亡159例,中位生存时间为12(2～18)个月,2组差异有统计学意义(x2=11.04,P=0.001).经Cox多因素分析,ProGRP为影响SCLC患者总生存(OS)的独立预后因素(ward=18.35,OR =4.12,p=0.000).结论 血清ProGRP水平可评价SCLC患者治疗疗效和预后,治疗后密切随访ProGRP,对高危复发SCLC患者的识别和转移病灶的发现有指导意义.
目的 探討血清胃泌素前體釋放肽(ProGRP)對小細胞肺癌(SCLC)療效鑑測的臨床意義,評估ProGRP水平與SCLC預後的關繫.方法 臨床診斷研究.用ELISA檢測2005年12月至2008年10月期間山西省腫瘤醫院呼吸與放療科治療、有完整資料的SCLC患者413例,非小細胞肺癌(NSCLC)418例、良性疾病患者120例及200名健康人的血清ProGRP、NSE水平.2005年12月至2011年10月隨訪368例SCLC患者ProGRP水平.以413例SCLC患者標本繪製ProGRP、NSE受試者工作特徵麯線(ROC)；Kaplan-Meier法分析SCLC患者生存時間,Cox比例風險模型分析影響SCLC患者預後的因素.結果 ProGRP診斷SCLC的ROC麯線AUC為0.798(95％ CI:0.746 ～0.850),以45.3 μg/L為臨界值,其敏感度、特異度分彆為79.2％,98.1％；NSE診斷SCLC的ROC麯線AUC為0.786 (95％ CI:0.726 ～0.746),以12.4 μg/L為臨界值,其敏感度、特異度分彆為71.9％,96.7％；ProGRP與NSE聯閤診斷SCLC的敏感度、特異度分彆為88.1％,95.8％.SCLC患者治療前血清ProGRP為1758.7(368.4 ～2967.3) μg/L,高于NSCLC患者組[21.3(18.6～35.2) μg/L]、肺良性疾病組[36.8(26.3 ～43.4) μg/L]和健康對照組[6.89(5.3～8.6) μg/L],差異有統計學意義(H=103.66,P=0.000).Ⅰ～Ⅱ期、Ⅲ期、Ⅳ期SCLC患者血清ProGRP分彆為543.3(256.8 ～ 843.2)、1440.6(1042.4 ～ 2543.3)、1897.6(1586.5 ～3958.7) μg/L,差異有統計學意義(H=25.974,P=0.000).完全緩解(CR)的165例患者治療後ProGRP水平[226.3(69.3 ～456.7) μg/L]比治療前[1025.2(436.8 ～1060.9) μg/L]明顯下降(U=11.65,P＜0.01)；部分緩解(PR)的146例患者治療後ProGRP水平[563.7(246.2 ～869.4)μg/L]與治療前[1351.5(859.5 ～1883.4) μg/L]相比有所下降(U =9.17,P＜0.01)；治療後病情無變化(NR)的63例患者[1575.6(1025.8～2596.5)μg/L]與病情進展(PD)的39例患者[2418.7(1869.2 ～4362.3)μg/L]與治療前ProGRP水平[分彆為1280.2(863.4～ 1968.7)、1867.6 (1689.3 ～3025.4) μg/L]相比,則明顯升高(U值分彆為3.314、2.54,P均＜0.01).隨訪至少3年的SCLC患者368例,隨訪率為89.1％(368/413).119例治療前ProGRP＜1000μg/L的SCLC患者死亡56例,中位生存時間為16(4 ～23)箇月,249例治療前ProGRP＞1000 μg/L SCLC患者死亡159例,中位生存時間為12(2～18)箇月,2組差異有統計學意義(x2=11.04,P=0.001).經Cox多因素分析,ProGRP為影響SCLC患者總生存(OS)的獨立預後因素(ward=18.35,OR =4.12,p=0.000).結論 血清ProGRP水平可評價SCLC患者治療療效和預後,治療後密切隨訪ProGRP,對高危複髮SCLC患者的識彆和轉移病竈的髮現有指導意義.
목적 탐토혈청위비소전체석방태(ProGRP)대소세포폐암(SCLC)료효감측적림상의의,평고ProGRP수평여SCLC예후적관계.방법 림상진단연구.용ELISA검측2005년12월지2008년10월기간산서성종류의원호흡여방료과치료、유완정자료적SCLC환자413례,비소세포폐암(NSCLC)418례、량성질병환자120례급200명건강인적혈청ProGRP、NSE수평.2005년12월지2011년10월수방368례SCLC환자ProGRP수평.이413례SCLC환자표본회제ProGRP、NSE수시자공작특정곡선(ROC)；Kaplan-Meier법분석SCLC환자생존시간,Cox비례풍험모형분석영향SCLC환자예후적인소.결과 ProGRP진단SCLC적ROC곡선AUC위0.798(95％ CI:0.746 ～0.850),이45.3 μg/L위림계치,기민감도、특이도분별위79.2％,98.1％；NSE진단SCLC적ROC곡선AUC위0.786 (95％ CI:0.726 ～0.746),이12.4 μg/L위림계치,기민감도、특이도분별위71.9％,96.7％；ProGRP여NSE연합진단SCLC적민감도、특이도분별위88.1％,95.8％.SCLC환자치료전혈청ProGRP위1758.7(368.4 ～2967.3) μg/L,고우NSCLC환자조[21.3(18.6～35.2) μg/L]、폐량성질병조[36.8(26.3 ～43.4) μg/L]화건강대조조[6.89(5.3～8.6) μg/L],차이유통계학의의(H=103.66,P=0.000).Ⅰ～Ⅱ기、Ⅲ기、Ⅳ기SCLC환자혈청ProGRP분별위543.3(256.8 ～ 843.2)、1440.6(1042.4 ～ 2543.3)、1897.6(1586.5 ～3958.7) μg/L,차이유통계학의의(H=25.974,P=0.000).완전완해(CR)적165례환자치료후ProGRP수평[226.3(69.3 ～456.7) μg/L]비치료전[1025.2(436.8 ～1060.9) μg/L]명현하강(U=11.65,P＜0.01)；부분완해(PR)적146례환자치료후ProGRP수평[563.7(246.2 ～869.4)μg/L]여치료전[1351.5(859.5 ～1883.4) μg/L]상비유소하강(U =9.17,P＜0.01)；치료후병정무변화(NR)적63례환자[1575.6(1025.8～2596.5)μg/L]여병정진전(PD)적39례환자[2418.7(1869.2 ～4362.3)μg/L]여치료전ProGRP수평[분별위1280.2(863.4～ 1968.7)、1867.6 (1689.3 ～3025.4) μg/L]상비,칙명현승고(U치분별위3.314、2.54,P균＜0.01).수방지소3년적SCLC환자368례,수방솔위89.1％(368/413).119례치료전ProGRP＜1000μg/L적SCLC환자사망56례,중위생존시간위16(4 ～23)개월,249례치료전ProGRP＞1000 μg/L SCLC환자사망159례,중위생존시간위12(2～18)개월,2조차이유통계학의의(x2=11.04,P=0.001).경Cox다인소분석,ProGRP위영향SCLC환자총생존(OS)적독립예후인소(ward=18.35,OR =4.12,p=0.000).결론 혈청ProGRP수평가평개SCLC환자치료료효화예후,치료후밀절수방ProGRP,대고위복발SCLC환자적식별화전이병조적발현유지도의의.
Objective The purpose of this study was to discuss the clinical significance of serum levels of Pro-gastrin-releasing peptide (ProGRP) in diagnosis,therapy monitoring and prognosis in patients with small cell lung cancer (SCLC).Methods Clinical diagnostic trial.Serum levels of ProGRP were measured by ELISA assays in 413 SCLC patients,418 NSCLC,120 with benign pulmonary diseases patients and 200 healthy subjects.Patients were recuited by the Shanxi Cancer Hospital from Dec.2005 to Oct.2008.Three hundreds and sixty-eight patients with SCLC were followed up from Dec.2005 to Oct.2011.The receiver operating characteristic curves (ROC) was used to set the cut-off value of ProGRP and the area under ROC (ROC-AUC).The sensitivity and specificity of ProGRP were analyzed for diagnosing SCLC.The survival analysis was performed by the Kaplan-Meier method and Cox's proportional hazards model for multivariate analysis of prognosis.Results Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off values of ProGRP and NSE (45.3 ng/L and 12.4 ng/L).The ROC-AUC of ProGRP was 0.798 (95％ CI:0.746-0.850)the sensitivity and specificity were 79.2％,98.1％ respectively.The AUC of NSE was 0.786(95％ CI:0.726-0.746),the sensitivity and specificity were 71.9％,96.7％ respectively; Combing detection of ProGRP and NSE,the sensitivity and specificity were 88.1％,95.8％ respectively.Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 6.9 (5.3-8.6),36.8 (26.3-43.4),21.3 (18.6-35.2) and 1758.7 (368.4-2967.3) μg/L respectively.The serum levels of ProGRP in SCLC groups were significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group (H =103.66,P =0.000).Serum levels of ProGRP in SCLC at stage Ⅰ-],stage m,stage Ⅳ were 543.3 (256.8-843.2),1440.6 (1042.4-2543.3) and 1897.6 (1586.5-3958.7) μg/L,respectively (H =25.974,P =0.000).Serum levels of ProGRP in 165 SCLC patients with complete remission(CR) were significantly declined after treatment (U =11.65,P ＜ 0.01).The levels of ProGRP in 146 SCLC patients with partial remission(PR) slowly decreased (U =9.17,P ＜ 0.01).Thirty-nine cases with progressive disease (PD)and 63 cases with stable disease(SD) presented elevated ProGRP levels (U =3.314,P ＜ 0.001 ; U =2.54,P ＜ 0.01,respectively).By the end of October 31st 2011,a total of 368 cases with SCLC were followedup.Ratio of follow-up was 89.1％.There were 56 deaths in 119 SCLC patients with ProGRP ＜ 1000 μg/L (median time =16.0 months,4-23 months) ; 159 deaths in 249 with ProGRP ＞ 1000 μg/L (median survival time =12.0 months,2-18 months).Median survival time of the two groups showed significant differences(x2 =11.04,P =0.001).Multivariate analysis by Cox's proportional hazards model revealed that ProGRP was independent prognostic factor related to the overall survival (OS) of SCLC patients.Conclusions The serum ProGRP is valuable tumor marker for diagnosis,treat monitoring and prognosis of SCLC.It's important to predict relapses and recurrence of diseases earlier,instruct therapy and prognosis assessment.
