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非小细胞肺癌患者治疗前血清 CEA和 CYFRA21-1水平与 EGFR 突变及 EGFR-TKI 疗效的关系 被引量:29

Serum CEA and CYFRA21-1 correlates with EGFR mutation and EGFR-TKI effectiveness in untreated NSCLC patients
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摘要 目的:探讨非小细胞肺癌患者治疗前血清CEA和细胞角蛋白19( CYFRA21-1)水平与表皮生长因子( EGFR)基因突变的相关性并分析其对酪氨酸激酶抑制剂( TKI)疗效的预测价值。方法本研究为临床研究,共收集北京大学人民医院2012至2013年101例非小细胞肺癌患者配对癌组织和外周血标本。采用ADx-ARMS法和直接测序法检测上述标本EGFR基因18、19、20、21外显子基因突变,同时采用电化学发光方法检测患者血清CEA和CYFRA21-1表达水平。采用χ2检验、Log-rank检验和cox回归,分析患者肿瘤标志物水平与EGFR突变和EGFR-TKI疗效的关系。结果双环探针扩增阻滞突变系统(ADx-ARMS)总突变检出率为60.4%(61/101),直接测序法为33.7%(34/101)。突变多见于治疗前血清CEA浓度升高(≥5μg/L,78.8%)患者,但突变率不随CEA浓度增加而升高。靶向治疗疗效方面,治疗前血清CYFRA21-1水平和EGFR突变状态与TKI治疗的无进展生存期(PFS)相关(χ2=8.903,P=0.003;χ2=28.590,P<0.001),同时也是影响靶向治疗患者PFS的独立因素( RR=0.298,P<0.001;RR=0.086,P<0.001)。结论治疗前CEA浓度与EGFR突变相关,同时可与CYFRA21-1作为预测非小细胞肺癌接受EGFR-TKI治疗的疗效指标。(中华检验医学杂志,2015,38:407-411) Objective To explore the predictive value of serum CEA and cytokeratin-19 fragments (CYFRA21-1)prior treatment for the epidermal growth factor receptor (EGFR) mutation and efficacy of tyrosine kinase inhibitors ( TKI ) in patients with non-small cell lung cancer.Methods The study was a clinical research.Totally 101 matched tissue and plasma samples were collected from Peking University People′s Hospital from 2012 to 2013.All clinical specimens were analyzed for EGFR mutations in exons of 18, 19, 20 and 21 by ADx-ARMS and direct sequencing, and the serum levels of CEA and CYFRA21-1 were analyzed by ECLI.The correlation between EGFR mutant status and efficacy of EGFR-TKI and clinicopathological parameters were analyzed by χ2 test, Log-rank text and Cox proportional hazards regression model.Results The mutation rate was 60.4%(61/101) by ADx-ARMS and 33.7%(34/101) by direct sequencing.Mutations were more frequently observed in the higher serum CEA level patients(≥5μg/L,78.8%).However, the rates of EGFR mutations of different CEA levels were similar.Among the patients receiving TKI therapy, the efficacy of EGFR-TKI was closely related to serum CYFRA21-1 level prior treatment and EGFR mutation (χ2 =8.903, P =0.003; χ2 =28.590, P 〈0.001 ).And serum CYFRA21-1 level prior treatment and EGFR mutation were independent factors for EGFR-TKI treatment affecting PFS (RR=0.298, P〈0.001;RR=0.086, P〈0.001).Conclusion The mutation rate of EGFR was significantly related with the expression level of CEA prior treatment, and serum CEA and CYFRA21-1 levels prior treatment could be potential predictors of EGFR-TKI efficacy.
出处 《中华检验医学杂志》 CAS CSCD 北大核心 2015年第6期407-411,共5页 Chinese Journal of Laboratory Medicine
关键词 非小细胞肺 癌胚抗原 抗原 肿瘤 角蛋白19 受体 表皮生长因子 Keratin-19 Carcinoma,non-small-cell lung Carcinoembryonic antigen Antigens,neoplasm Receptor,epidermal growth factor
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  • 1Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin, 2005, 55(2) : 74-108.
  • 2Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA Cancer J Clin, 2010, 60(5) : 277-300.
  • 3Green MR. Targeting targeted therapy[J]. N Engl J Med, 2004, 350(21) : 2191-2193.
  • 4MassareUi E, Andre F, Liu DD, et al. A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small- cell lung eancer[J]. Lung Cancer, 2003, 39(1 ) : 55-61.
  • 5Xue C, Hu Z, Jiang W, et al. National survey of the medical treatment status for non-small cell lung cancer (NSCLC) in China [J]. Lung Cancer, 2012, 77(2) : 371-375.
  • 6Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy [ J ]. Science, 2004, 304(5676) : 1497-1500.
  • 7Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib[ J]. N Engl J Med, 2004, 350(21 ) : 2129-2139.
  • 8Pao W, Ladanyi M. Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method [ J]. Clin Cancer Res, 2007, 13(17): 4954-4955.
  • 9孙艳丽,李金明.Kras、EGFR、BRAF基因突变检测及其应用研究进展[J].中华检验医学杂志,2012,35(11):971-977. 被引量:5
  • 10Ogino S, Kawasaki T, Brahmandam M, et al. Sensitive Sequencing Method for < i > KRAS </i > Mutation Detection by Pyrosequencing[J]. J Mol Diagn, 2005, 7(3) : 413-421.

二级参考文献46

  • 1Gibson WM. Can personalized medicine survive. Can FamPhysician, 1971,17:29-88.
  • 2Langreth R, Waldholz M. New era of personalized medicine:targeting drugs for each unique genetic profile. Oncologist, 1999 ,4:426-427.
  • 3Meyer UA. Genotype or phenotype: the definition of apharmaoogenetic polymorphism. Pharmacogenetics, 1991 , 1 : 66-67.
  • 4Maitland ML,Vasisht K’Ratain MJ. TPMT,UGTiAl and DPYD:genotyping to ensure safer cancer therapy . Trends Pharmacol Sci,2006,27:432437.
  • 5Tam IY, Chung LP, Suen WS, el a]. Distinct epidermal growthfactor receptor and KRAS mutation patterns in non-small cell lungcancer patients with different tobacco exposure andclinicopathologio features. Clin Cancer Res ,2006,12 : 1647-1653.
  • 6Ahmad El,Gawish HH,Al Azizi NM,et al. The prognostic impaclof K-RAS mutations in adult acute myeloid leukemia palienlstreated with high-dose cytarabine. Onco Targets Ther, 2011 , 4 :115-121.
  • 7Almoguera C, SKibata D, Forrester K, et al. Most humancarcinomas of the exocrine pancreas contain mutant c-K-ras genes.Cell, 1988,53 :549-554.
  • 8Burmer GC,Loeb LA. Mutations in the KRAS2 oncogene duringprogressive stages of human colon carcinoma. Proc* Natl Acad SciU S A,1989,86:2403-2407.
  • 9Schubbert S,Zenker M,Rowe SL,et al. Germline KRAS mutationscause Noonan syndrome. Nat Genet ,2006,38 :331 -336.
  • 10Niihori T, Aoki Y, Narumi Y, et al. Germline KRAS and BRAFmutations in cardio-facio-cutaneous syndrome. Nat Genet, 2006,38 :294-296.

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