肺癌标志物筛查和癌症风险评估

1、肺癌标志物筛查与癌症风险评估,癌症面临的严峻形势,肿瘤标志物应用于癌症筛查和风险评估,早期识别高危人群,缩短癌症诊断周期,总结,全球男性,新发病例,死亡病例,肺和支气管癌,109.52,万,前列腺癌,90.35,万,结肠,直肠癌,66.36,万,胃癌,64.06,万,肝癌,52.24,万,食管癌,32.66,万,膀胱癌,29.73,万,肺和支气管癌,95.10,万,肝癌,47.83,万,胃癌,46.44,万,结肠,直肠癌,32.06,万,食管癌,27.61,万,前列腺癌,25.84,万,白血病,14.37,万,死亡,新发：肺癌,86.8,前列腺癌,28.6,截至,2012,年，中国,22.08

2、,的人患有癌症,12.94,的人,死于癌症,2012,中国肿瘤登记年报,2012,世界癌症日,面对癌症,我们能做什么,早期识别高危人群,需求,1,高风险人群,低风险人群,表观健康人群,门诊患者,一管血检测肿瘤标志物,能否有助于癌症的风险评估,肿瘤标志物在,肺癌,风险评估中的实践应用,ProGRP/NSE,小细胞肺癌,CYFRA 21-1,非小细胞肺癌,SCC,肺鳞癌,CEA,肺腺癌,多联肺癌标志物,针对于高危人群（吸烟,人群）及出现疑似肺癌症状（咳血，胸痛,肺部肿物）的患者进行肺癌筛查,非小细胞肺癌,NSCLC,CEA,SCC,Cyfra,小细胞肺癌,SCLC,ProGRP,NSE,CEA,灵

3、敏度,NSCLC 82,SCLC 80,特异性,92,未提供除肿瘤标志物结果以外的其他信息,运用肺癌肿瘤标志物检测组,ProGRP+SCC+CYFRA21-1+CEA,评估罹患,肺癌的风险,N=155,表观健康人群,N=6,良性肺病,N,42,肺癌,N=107,NSCLC N,91,SCLC N=16,6/6,健康标本被评价为低危,32/42,良性疾病标本被评价为低危,96/107,恶性标本被评价为高危,数据来源：上海中山医院呼吸科,Role of progestrin releasing peptide (ProGRP), a serum based biomarker in early d

4、iagnosis of SCLC in cohort of high risk patient,presenting with symptoms related,to lung Caner,Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai,2012 Asian Pacific Society of Respirology Congress Poster,ProGRP+SCC+CYFRA21-1+CEA,肺癌,N=64,CT,阳性,50,14,CT,阴

5、性,肺癌标志物检测组,阳性,肺癌标志物检测组,阴性,8,8/14=57,6,敏感性,81.2,52/64,90.6,58/64,78.1,50/64,肺癌标志物检测组,CT,肺癌标志物检测组,CT,表：确诊为肺癌的,64,名病例,联合肺癌标志物检测组将,CT,的肺癌检出率从,78.1,提高到,90.6,ProGRP+SCC+CEA+CYFRA21-1,Role of progestrin releasing peptide (ProGRP), a serum based biomarker in early diagnosis of SCLC in cohort of high risk pa

6、tient,presenting with symptoms related,to lung Caner,Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Fudan University, Shanghai,2012 Asian Pacific Society of Respirology Congress Poster,N,761,例,肿瘤患者,Molina R, Auge JM, Bosch X, et al,Tumor Biol,2009,30:121-9,NSCLC,SP:97.2,SN:76

7、.7,PPV:98.6,SCLC,SP:99.6,SN:79.5,PPV:98.6,Molina R, Auge JM, Bosch X, et al,Tumor Biol,2009,30:121-9,Percent of untreated lung cancer patients with serum tumor marker levels greater than the cutoff, categorized according to histology and,tumor extension,ADK: Adenocarcinoma,LCLC: Large cell lung canc

8、er,ProGRP,应用于小细胞肺癌诊断最灵敏,CYFRA21-1,是针对非小细胞肺癌最敏感的标志物,Clinical conditions,N,Plasma proGRP,平均值,pg/mL,健康,49,42.5,良性疾病,23,40.1,肺癌,SCLC,37,1367.5,NSCLC,116,56.3,鳞癌,59,38.7,腺癌,40,59.2,未分型,NSCLC,12,35.2,大细胞癌,5,290.9,继发转,移性癌,2,34.3,J Korean Med Sci 2011; 26: 625-630,ProGRP,是小细胞肺癌的一个非常可靠的指标,具有很好的灵敏度,和特异性,非常有助于

9、组织分型,当单独使用,时,要远优于,NSE,NSE,对于筛查而言,缺少灵敏度和特异性,高,浓度的,NSE,也只是怀,疑有小细胞肺癌,缺少特异性,很多文献建议,使,用,NSE,在诊断,SCLC,的时候要结合,ProGRP,溶血标本中,NSE,会产生检测值假性升高,美国国家临床生化协会,男性,69,岁,已戒烟。因,X,线发现肺部单个肿块入院,所有肿瘤标志物结果正常，提示非癌性肿块,可能性大,75,肺癌肿瘤标志物异常，但,15%-25,的肺癌患者的肿瘤标,志物可能正常（取决于分期和病理类型,最终诊断,肉芽肿,肌酐,0.9,mg/dl,GGT,23,U/L,AST,17,U/L,ALT,15,U/L,

10、CEA,1.5,ng/ml,CYFRA,0.8,ng/ml,SCC,0.6,ng/ml,NSE,11,ng/ml,ProGRP 12 pg/ml,CA 125,19,U/ml,CA 15.3,6,U/ml,CA 19.9,15,U/ml,CEA, 5,ng/mL,CYFRA, 3,3,ng/mL,SCC, 2,5,ng/mL,CA 125, 40,U/mL,CA 15.3, 35,U/mL,CA 19.9, 37,U/mL,TAG, 6,U/mL,NSE, 25,ng/mL,ProGRP, 50,pg/mL,男性,65,岁,已戒烟。因呼吸短促入院。既往有,COPD,糖尿病，高血压病史,ProG

11、RP,和,NSE,升高尤为明显，高度提示,SCLC,最终诊断,SCLC,肌酐,1.5,mg/dl,GGT,35,U/L,AST,56,U/L,ALT,29,U/L,CEA,5,ng/ml,CYFRA,6.8,ng/ml,SCC,0.4,ng/ml,NSE,370,ng/ml,ProGRP 1093 pg/ml,CA 125,19,U/ml,CA 15.3,77,U/ml,CA 19.9,10,U/ml,CEA, 5,ng/mL,CYFRA, 3,3,ng/mL,SCC, 2,5,ng/mL,CA 125, 40,U/mL,CA 15.3, 35,U/mL,CA 19.9, 37,U/mL,TA

12、G, 6,U/mL,NSE, 25,ng/mL,ProGRP, 50,pg/mL,患者，男性,55,岁，确诊,SCLC,检测血,ProGRP,进行随访监测，病情出现恶化,ProGRP,明显升高,334.07,升高至,1813.45pg/ml,，之后开始放疗，病情缓解,ProGRP,明显下降,缩短癌症诊断周期,需求,2,肺癌早期无症状和症状轻微,2/3,的患者在发现时已处于扩散阶段，五年,存活率小于,5,如在早期发现，通过手术治疗，五年存活,率高达,70,80,治疗越早，预后越好,预后的关键在于早期检出，早期治疗,X-ray (First Test Ordered,CT Scan,核磁共振,PE

13、T,活检,目前的金标准,痰液细胞学,支气管镜检,胸镜,Tyson LB. Non-small cell lung cancer. In Houlihan N, editor. Lung Cancer. Pittsburgh: Oncology Nursing Society; 2004. p 83-102,肿瘤大小,2mm,可被标志物,检出,肺癌启动,肺癌导致死亡,大约,10,年,潜伏期,大约,2,年,临床期,诊断,关键点,可实现有效筛查,Ref: F. Olesen, British Journal of Cancer (2009) 101, S5,S8,从首次症状出现到确诊：需要,30 -

14、120,天,当前诊断流程时间较长,Biopsy,Physical,Exam,X-Ray,CT SCAN,Bronchoscopy,Risk,Assessment,The most important risk factor is tobacco use,X-ray is the most universal approach,Detect location of a tumor,Visualizing the inside,of airway for tumors,Gold Standard,To test lung function,14,60,天,Ref: Tumor Markers in

15、 Lung Cancer: Theory and Practice by Dr. Rafael Molina,血清学危险评估能够帮助缩短确诊时间,Biopsy,Physical,Exam,X-Ray,LAB TEST,Bronchoscopy,CT Scan,Risk,Assessment,5,天,Patient,Oncologist,Day 1,Ref: Tumor Markers in Lung Cancer: Theory and Practice by Dr. Rafael Molina,对于,40,的具有症状的非癌症患者的诊,断给予支持,对于,5%-10,的误判给予纠正,Creatinin,0,9 mg/dl,ALAT,21 U/L,GGT,21 U/L,LDH,907 U/L,CEA,31.9 ng/ml,CYFRA,11.9 ng/ml,SCC,0.5 ng/ml,CA 125,63 U/ml,CA 15.3,26 U/ml,CA 19.9,37 U/ml,TAG,1,2 ng/ml,NSE,169 ng/ml,ProGRP,1835 pg/ml,最终诊断：小细胞肺癌,肺部,X,线支持为支气管肺炎，实验室根据肿