肺癌早期诊断相关新型标志物的研究进展_West China Medical Journal

Authors：

麦琳 , 孙蓉菲 ,  李为民

Corresponding author：

李为民, Email: mailin_2012@sina.com

Keywords：

肺癌; 标志物; 早期诊断

DOI：

10.7507/1002-0179.20130152

Video：

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Abstract Full text Figures/Tables Video References Cited by

肺癌是人类最常见的肿瘤之一。目前用于肺癌早期筛查主要包括X线、胸部CT及血清肿瘤标志物（如癌胚抗原、神经元烯醇化酶、细胞角蛋白19片段等），但其敏感性及特异性均不尽人意。目前新发现的肿瘤相关自身抗体/抗原中，大部分并没有较好的敏感性。相比早期诊断，循环中肿瘤细胞在测预后中更有意义。有文献系统评价总结了在非小细胞肺癌中，治疗前和治疗后检测循环中肿瘤细胞对预后的HR值分别为2.61（1.82、3.74）或4.19 （2.92、6.00）。大量的研究提示血液、呼出气体及痰中蛋白组学、小核苷酸分子及DNA片段检测有较大潜力，尤其是检测血液不同组合的小核苷酸分子可能有更好的效果。现参考近年文献就新型肺癌早期检测的方式作一综述。

Citation： 麦琳,孙蓉菲,李为民. 肺癌早期诊断相关新型标志物的研究进展. West China Medical Journal, 2013, 28(3): 466-472. doi: 10.7507/1002-0179.20130152 Copy

1.	段纪俊, 陈万青, 张思维. 中国恶性肿瘤死亡率的国际比较[J]. 中国社会医学杂志, 2009, 26(6): 377-378.
2.	Chen WQ, Zhang SW, Zou XN. Evaluation on the incidence, mortality and tendency of lung cancer in China [J]. Thoracic Cancer, 2010, 1(1): 35-40.
3.	Van’t Westeinde SC, van Klaveren RJ. Screening and early detection of lung cancer [J]. Cancer J, 2011, 17(1): 3-10.
4.	Fujikawa A, Takiguchi Y, Mizuno S, et al. Lung cancer screening--comparison of computed tomography and X-ray [J]. Lung Cancer, 2008, 61(2): 195-201.
5.	卢先锋, 杨雪琴, 张志敏, 等. 肺癌血清肿瘤标志物meta分析[J]. 中国肺癌杂志, 2010, 13(12):1136-1140.
6.	赵肖, 王孟昭. 肺癌血清肿瘤标志物的临床意义[J]. 中国肺癌杂志, 2011, 14(3): 286-291.
7.	Xie Y, Todd NW, Liu Z, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer[J]. Lung Cancer, 2010, 67(2): 170-176.
8.	Neumann T, Meyer M, Patten FW, et al. Premalignant and malignant cells in sputum from lung cancer patients[J]. Cancer, 2009, 117(6): 473-481.
9.	姜勇, 晋萍, 常润生, 等. 肺癌不同阳性标准痰细胞学筛查方法的灵敏度和特异度分析[J]. 中华预防医学杂志, 2011, 45(7): 605-608.
10.	Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape[J]. Nat Immunol, 2002, 3(11): 991-998.
11.	Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting [J]. Annu Rev Immunol, 2004, 22: 329 -360.
12.	Belousov PV, Kuprash DV, Nedospasov SA, et al. Autoantibodies to tumor-associated antigens as cancer biomarkers [J]. Current Mol Med, 2010, 10(2):115-122.
13.	Zhang JY, Tan EM. Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors [J]. Expert Rev Mol Diagn, 2010, 10(3): 321-328.
14.	Liu W, Peng B, Lu Y, et al. Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis[J]. Autoimmun Rev, 2011, 10(6): 331-335.
15.	Straten Pt, Andersen MH. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens[J]. Oncotarget, 2010, 1(4): 239-245.
16.	Alias A, Rodriguez EJ, Bateman HE, et al. Rheumatology and oncology: an updated review of rheumatic manifestations of malignancy and anti-neoplastictherapy[J]. Bull NYU Hosp Jt Dis, 2012, 70(2): 109-114.
17.	姚毅冰. 肿瘤自身抗体在肺癌早期诊断中的作用[J]. 中国肺癌杂志, 2010, 13(9): 903-907.
18.	Wu L, Chang W, Zhao J, et al. Development of autoantibody signatures as novel diagnostic biomarkers of non-small cell lung cancer. Development of autoantibody signatures as novel diagnostic biomarkers of non-small cell lung cancer [J]. Clin Cancer Res, 2010, 16(14): 3760-3768.
19.	Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma [J]. Cancer Res, 2007, 67(7): 3461-3467.
20.	Boyle P, Chapman CJ, Holdenrieder S, et al. Clinical validation of an autoantibody test for lung cancer [J]. Ann Oncol, 2011, 22(2): 383-389.
21.	Cherneva R, Petrov D, Georgiev O, et al. Clinical usefulness of alpha-crystallin antibodies in non-small cell lung cancer patients[J]. Interact Cardiovasc Thorac Surg, 2010, 10(1): 14-17.
22.	Khattar NH, Coe-Atkinson SP, Stromberg AJ, et al. Lung cancer-associated auto-antibodies measured using seven amino acid peptides in a diagnostic blood test for lung cancer [J]. Cancer Biol Ther, 2010, 10(3): 267-272.
23.	Chapman CJ, Murray A, McElveen JE, et al. Autoantibodies in lung cancer: possibilities for early detection and subsequent cure [J]. Thorax, 2008, 63(3): 228-233.
24.	Qiu J, Choi G, Li L, et al. Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera [J]. J Clin Oncol, 2008, 26(31): 5060-5066.
25.	Pereira-Faca SR, Kuick R, Puravs E, et al. Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer [J]. Cancer Res, 2007, 67(24): 12000-12006.
26.	Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronicgene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell, 1993, 75(5): 843-854.
27.	Wiemer EA. The role of microRNAs in cancer: No small matter [J]. Eur J Cancer, 2007, 43(10): 1529-1544.
28.	Xing L, Todd NW, Yu L, et al. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers [J]. Mod Pathol, 2010, 23(8):1157-1164.
29.	Shen J, Todd NW, Zhang H, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer[J]. Lab Invest, 2011, 91(4): 579-587.
30.	Hennessey PT, Sanford T, Choudhary A, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer[J]. PLoS One, 2012, 7(2): e32307.
31.	Chu H, Wang M, Shi D, et al. Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies [J]. PLoS ONE, 2011, 6(3): e18108.
32.	Bishop JA, Benjamin H, Cholakh H, et al. Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach [J]. Clin Cancer Res, 2010, 16(2): 610-619.
33.	Landi MT, Zhao Y, Rotunno M, et al. MicroRNA expression differentiates histology and predicts survival of lung cancer [J]. Clin Cancer Res, 2010, 16(2): 430-441.
34.	Shen J, Liu Z, Todd NW, et al. Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers [J]. BMC Cancer, 2011, 11(1): 374.
35.	Zheng D, Haddadin S, Wang Y, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer [J]. Int J Clinical Exp Pathol, 2011, 4(6): 575-586.
36.	Leidinger P, Keller A, Borries A, et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD [J]. Lung Cancer, 2011, 74(1): 41-47.
37.	Criscitiello C, Sotiriou C, Ignatiadis M. Circulating tumor cells and emerging blood biomarkers in breast cancer [J]. Curr Opin Oncol, 2010, 22(6): 552- 558.
38.	Sevli S, Uzumcu A, Solak M. The function of microRNAs, small but potent molecules, in human prostate cancer [J]. Prostate Cancer Prostatic Dis, 2010, 13(3): 208-217.
39.	Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers[J]. Med Res Rev, 2012, 32(2): 326-348.
40.	Hou JM, Krebs MG, Lancashire L, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer [J]. J Clin Oncol, 2012, 30(5): 525-532.
41.	Li Q, Qi H, Zhou HX, et al. Detection of micrometastases in peripheral blood of non-small cell lung cancer with a refined immunomagnetic nanoparticle enrichment assay [J]. Int J Nanomedicine, 2011, 6: 2175-2181.
42.	Bartling B, Hofmann HS, Sohst A, et al. Prognostic potential and tumor growth-inhibiting effect of plasma advanced glycation end products in non-small cell lung carcinoma [J]. Mol Med, 2011, 17(9-10): 980-989.
43.	Krebs MG, Hou JM, Sloane R, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches[J]. J Thorac Oncol, 2012, 7(2): 306-315.
44.	Hofman V, Ilie MI, Long E, et al. Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the Cell Search AssayTM and the isolation by size of epithelial tumor cell method [J]. Int J Cancer, 2011, 129(7): 1651-1660.
45.	Ma XL, Xiao ZL, Liu L，et al. Meta-analysis of circulating tumor cells as a prognostic marker in lung cancer[J]. Asian Pac J Cancer Prev, 2012, 13(4): 1137-1144.
46.	Devriese LA, Bosma AJ, van de Heuvel MM, et al. Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis[J]. Lung Cancer, 2012, 75(2): 242-247.
47.	Kato H, Nishimura T, Hirano T, et al. A clinician view and experience of proteomic studies in the light of lung cancer in Japanese healthcare[J]. J Proteome Res, 2011, 10(1): 51-57.
48.	Ostroff RM, Bigbee WL, Franklin W, et al. Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer [J]. PLoS One, 2010, 5(12): e15003.
49.	Cremona M, Calabrò E, Randi G, et al. Elevated levels of the acute-phase serum amyloid are associated with heightened lung cancer risk [J]. Cancer, 2010, 116(5): 1326-1335.
50.	张恒, 陈胜喜, 黄凌瑾, 等. 非小细胞肺癌血清标志物PACAP的蛋白质组学筛选和鉴定[J]. 中国肺癌杂志, 2012, 15(5): 287-293.
51.	Yang J, Song YC, Song TS, et al. Identification of novel low molecular weight serum peptidome biomarkers for non-small cell lung cancer (NSCLC) [J]. J Clin Lab Anal, 2012, 26(3): 148-154.
52.	Du J, Yang SY, Lin XL, et al. Biomarker discovery and identification from non-small cell lung cancer sera[J]. Front Biosci (Elite Ed), 2011, 3: 1-10.
53.	Patz EF Jr, Campa MJ, Gottlin EB, et al. Panel of serum biomarkers for the diagnosis of lung cancer [J]. J Clin Oncol, 2007, 25(35): 5578-5583.
54.	Sreseli RT, Binder H, Kuhn M, et al. Identification of a 17-protein signature in the serum of lung cancer patients[J]. Oncol Rep, 2010, 24(1): 263-270.
55.	Kumar S, Guleria R, Singh V, et al. Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy[J]. Lung cancer, 2010, 70(2): 211-217.
56.	Paci M, Maramotti S, Bellesia E, et al. Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer[J]. Lung cancer, 2009, 64(1): 92-97.
57.	Begum S, Brait M, Dasgupta S, et al. An epigenetic marker panel for detection of lung cancer using cell-free serum DNA [J]. Clin Cancer Res, 2011, 17(13): 4494-503.
58.	Ulivi P, Zoli W, Calistri D, et al. p16INK4A and CDH13 hypermethylation in tumor and serum of non-small celllung cancer patients [J]. J Cell Physiol, 2006, 206(3): 611-615.
59.	刘晋祎, 安倩, 许冠东, 等. 肺癌患者外周血血浆中p16基因异常甲基化的检测[J]. 中国肿瘤杂志, 2004, 26(3): 154-157.
60.	Tsao DA, Yang MJ, Chang HJ, et al. A fast and convenient new technique to detect the therapeutic target, K-ras mutant, from peripheral blood in non-small cell lung cancer patients [J]. Lung Cancer, 2010, 68(1): 51-57.
61.	Ramirez JL, Sarries C, de Castro PL, et al. Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small cell lung cancer patients [J]. Cancer Lett, 2003, 193(2): 207-216.
62.	Beau-Faller M, Gaub MP, Schneider A, et al. Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer Patients[J]. Int J Cancer, 2003, 105(3): 361-370.
63.	Sozzi G, Musso K, Ratcliffe C, et al. Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis [J]. Clin Cancer Res, 1999, 5(10): 2689-2692.
64.	Vinayanuwattikun C, Sriuranpong V, Tanasanvimon S, et al. Epithelial-specific methylation marker: a potential plasma biomarker in advanced non-small cell lung cancer[J]. J Thorac Oncol, 2011, 6(11): 1818-1825.
65.	Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath[J]. BMC Cancer, 2009, 9(1): 348.
66.	Ligor M, Ligor T, Bajtarevic A, et al. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry [J]. Clin Chem LabMed, 2009, 47(5): 550-560.
67.	Fuchs P, Loeseken C, Schubert JK, et al. Breath gas aldehydes as biomarkers of lung cancer [J]. Int J Cancer, 2010, 126(11): 2663-2670.
68.	Skeldon KD, McMillan LC, Wyse CA, et al. Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer [J]. Res Med, 2006, 100(2): 300-306.
69.	刘虎, 宋耕, 秦涛, 等. 非小细胞肺癌患者呼气中挥发性有机化合物的定量分析[J]. 中华肿瘤防治杂志, 2009, 16(23): 1857-1859.
70.	Han W, Wang T, Reilly AA, et al. Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients [J]. Respir Res, 2009, 10(1): 86.
71.	Carpagnano GE, Foschino-Barbaro MP, Mulé G, et al. 3p micro satellite alterations in exhaled breath condensate from patients with non-small cell lung cancer [J]. Am J Respir Crit Care Med, 2005, 172(6): 738-744.
72.	Carpagnano GE, Foschino-Barbaro MP, Spanevello A, et al. 3p microsatellite signature in exhaled breath condensate and tumor tissue of patients with lung cancer [J]. Am J Respir Crit Care Med, 2008, 177(3): 337-341.
73.	Carpagnano GE, Spanevello A, Carpagnano F, et al. Prognostic value of exhaled microsatellite alterations at 3p in NSCLC patients[J]. Lung Cancer, 2009, 64(3): 334-340.
74.	Jungraithmayr W, Frings C, Zissel G, et al. Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma[J]. Respirology, 2008, 13(7): 1022-1027.
75.	陈金亮, 陈建荣, 陶一江, 等. 慢性阻塞性肺疾病患者呼出气冷凝液中白细胞三烯B4和肿瘤坏死因子-α的检测及其临床意义[J]. 中国危重病急救医学, 2008, 20(6): 357-360.
76.	Barta I, Kullmann T, Csiszer E, et al. Analysis of cytokine pattern in exhaled breath condensate of patients with squamous cell lung carcinoma [J]. Int J Biol Markers, 2010, 25(1): 52-56.
77.	Gessner C, Rechner B, Hammerschmidt S, et al. Angiogenic markers in breath condensate identify non-small cell lung cancer[J]. Lung Cancer, 2010, 68(2): 177-184.
78.	Carpagnano GE, Spanevello A, Curci C, et al. IL-2, TNF-alpha, and leptin: local versus systemic concentrations in NSCLC patients[J]. Oncol Res, 2007, 16(8): 375-381.
79.	Carpagnano GE, Spanevello A, Palladino GP, et al. Cigarette smoke and increased COX-2 and survivin levels in exhaled breath condensate of lung cancer patients: how hot is the link?[J]. Lung Cancer, 2010, 67(1): 108-113.
80.	Barash O, Peled N, Hirsch FR, et al. Sniffing the unique “odor print” of non-small-cell lung cancer with gold nanoparticles[J]. Small, 2009, 5(22): 2618-2624.
81.	Jiang F, Todd NW, Li R, et al. A panel of sputum-based genomic marker for early detection of lung cancer [J]. Cancer Prev Res, 2010, 3(12):1571-1578.
82.	Jiang F, Todd NW, Qiu Q, et al. Combined genetic analysis of sputum and computed tomography for noninvasive diagnosis of non-small-cell lung cancer [J]. Lung Cancer, 2009, 66(1): 58-63.
83.	Dimakou K, Hillas G, Bakakos P. Adenosine deaminase activity and its isoenzymes in the sputum of patients with pulmonary tuberculosis[J]. Int J Tuberc Lung Dis, 2009, 13(6): 744-748.
84.	Yu L, Todd NW, Xing L, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers [J]. Int J Cancer, 2010, 127(12): 2870-2878.
85.	李红梅, 付军桦, 修元德. 端粒酶与CYFRA21-1联合测定对肺癌所致恶性胸腔积液同良性胸腔积液鉴别的诊断意义[J]. 中国肺癌杂志, 2010, 13(6): 652-654.
86.	Xing L, Todd NW, Yu L, et al. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers [J]. Mod Pathol, 2010, 23(8): 1157-1164.
87.	Hsu HS, Chen TP, Wen CK, et al. Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment[J]. J Pathol, 2007, 213(4): 412-419.
88.	Hillas G, Moschos C, Dimakou K, et al. Carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 (CYFRA 21-1) levels in induced sputum of lung cancer patients[J]. Scand J Clin Lab Invest, 2008, 68(7): 542-547.
89.	Pio R, Garcia J, Corrales L, et al. Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer[J]. Cancer Epidemiol, Biomarkers Prev, 2010, 19(10): 2665-2672.

1. 　段纪俊, 陈万青, 张思维. 中国恶性肿瘤死亡率的国际比较[J]. 中国社会医学杂志, 2009, 26(6): 377-378.
2. 　Chen WQ, Zhang SW, Zou XN. Evaluation on the incidence, mortality and tendency of lung cancer in China [J]. Thoracic Cancer, 2010, 1(1): 35-40.
3. 　Van’t Westeinde SC, van Klaveren RJ. Screening and early detection of lung cancer [J]. Cancer J, 2011, 17(1): 3-10.
4. 　Fujikawa A, Takiguchi Y, Mizuno S, et al. Lung cancer screening--comparison of computed tomography and X-ray [J]. Lung Cancer, 2008, 61(2): 195-201.
5. 　卢先锋, 杨雪琴, 张志敏, 等. 肺癌血清肿瘤标志物meta分析[J]. 中国肺癌杂志, 2010, 13(12):1136-1140.
6. 　赵肖, 王孟昭. 肺癌血清肿瘤标志物的临床意义[J]. 中国肺癌杂志, 2011, 14(3): 286-291.
7. 　Xie Y, Todd NW, Liu Z, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer[J]. Lung Cancer, 2010, 67(2): 170-176.
8. 　Neumann T, Meyer M, Patten FW, et al. Premalignant and malignant cells in sputum from lung cancer patients[J]. Cancer, 2009, 117(6): 473-481.
9. 　姜勇, 晋萍, 常润生, 等. 肺癌不同阳性标准痰细胞学筛查方法的灵敏度和特异度分析[J]. 中华预防医学杂志, 2011, 45(7): 605-608.
10. 　Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape[J]. Nat Immunol, 2002, 3(11): 991-998.
11. 　Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting [J]. Annu Rev Immunol, 2004, 22: 329 -360.
12. 　Belousov PV, Kuprash DV, Nedospasov SA, et al. Autoantibodies to tumor-associated antigens as cancer biomarkers [J]. Current Mol Med, 2010, 10(2):115-122.
13. 　Zhang JY, Tan EM. Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors [J]. Expert Rev Mol Diagn, 2010, 10(3): 321-328.
14. 　Liu W, Peng B, Lu Y, et al. Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis[J]. Autoimmun Rev, 2011, 10(6): 331-335.
15. 　Straten Pt, Andersen MH. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens[J]. Oncotarget, 2010, 1(4): 239-245.
16. 　Alias A, Rodriguez EJ, Bateman HE, et al. Rheumatology and oncology: an updated review of rheumatic manifestations of malignancy and anti-neoplastictherapy[J]. Bull NYU Hosp Jt Dis, 2012, 70(2): 109-114.
17. 　姚毅冰. 肿瘤自身抗体在肺癌早期诊断中的作用[J]. 中国肺癌杂志, 2010, 13(9): 903-907.
18. 　Wu L, Chang W, Zhao J, et al. Development of autoantibody signatures as novel diagnostic biomarkers of non-small cell lung cancer. Development of autoantibody signatures as novel diagnostic biomarkers of non-small cell lung cancer [J]. Clin Cancer Res, 2010, 16(14): 3760-3768.
19. 　Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma [J]. Cancer Res, 2007, 67(7): 3461-3467.
20. 　Boyle P, Chapman CJ, Holdenrieder S, et al. Clinical validation of an autoantibody test for lung cancer [J]. Ann Oncol, 2011, 22(2): 383-389.
21. 　Cherneva R, Petrov D, Georgiev O, et al. Clinical usefulness of alpha-crystallin antibodies in non-small cell lung cancer patients[J]. Interact Cardiovasc Thorac Surg, 2010, 10(1): 14-17.
22. 　Khattar NH, Coe-Atkinson SP, Stromberg AJ, et al. Lung cancer-associated auto-antibodies measured using seven amino acid peptides in a diagnostic blood test for lung cancer [J]. Cancer Biol Ther, 2010, 10(3): 267-272.
23. 　Chapman CJ, Murray A, McElveen JE, et al. Autoantibodies in lung cancer: possibilities for early detection and subsequent cure [J]. Thorax, 2008, 63(3): 228-233.
24. 　Qiu J, Choi G, Li L, et al. Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera [J]. J Clin Oncol, 2008, 26(31): 5060-5066.
25. 　Pereira-Faca SR, Kuick R, Puravs E, et al. Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer [J]. Cancer Res, 2007, 67(24): 12000-12006.
26. 　Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronicgene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell, 1993, 75(5): 843-854.
27. 　Wiemer EA. The role of microRNAs in cancer: No small matter [J]. Eur J Cancer, 2007, 43(10): 1529-1544.
28. 　Xing L, Todd NW, Yu L, et al. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers [J]. Mod Pathol, 2010, 23(8):1157-1164.
29. 　Shen J, Todd NW, Zhang H, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer[J]. Lab Invest, 2011, 91(4): 579-587.
30. 　Hennessey PT, Sanford T, Choudhary A, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer[J]. PLoS One, 2012, 7(2): e32307.
31. 　Chu H, Wang M, Shi D, et al. Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies [J]. PLoS ONE, 2011, 6(3): e18108.
32. 　Bishop JA, Benjamin H, Cholakh H, et al. Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach [J]. Clin Cancer Res, 2010, 16(2): 610-619.
33. 　Landi MT, Zhao Y, Rotunno M, et al. MicroRNA expression differentiates histology and predicts survival of lung cancer [J]. Clin Cancer Res, 2010, 16(2): 430-441.
34. 　Shen J, Liu Z, Todd NW, et al. Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers [J]. BMC Cancer, 2011, 11(1): 374.
35. 　Zheng D, Haddadin S, Wang Y, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer [J]. Int J Clinical Exp Pathol, 2011, 4(6): 575-586.
36. 　Leidinger P, Keller A, Borries A, et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD [J]. Lung Cancer, 2011, 74(1): 41-47.
37. 　Criscitiello C, Sotiriou C, Ignatiadis M. Circulating tumor cells and emerging blood biomarkers in breast cancer [J]. Curr Opin Oncol, 2010, 22(6): 552- 558.
38. 　Sevli S, Uzumcu A, Solak M. The function of microRNAs, small but potent molecules, in human prostate cancer [J]. Prostate Cancer Prostatic Dis, 2010, 13(3): 208-217.
39. 　Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers[J]. Med Res Rev, 2012, 32(2): 326-348.
40. 　Hou JM, Krebs MG, Lancashire L, et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer [J]. J Clin Oncol, 2012, 30(5): 525-532.
41. 　Li Q, Qi H, Zhou HX, et al. Detection of micrometastases in peripheral blood of non-small cell lung cancer with a refined immunomagnetic nanoparticle enrichment assay [J]. Int J Nanomedicine, 2011, 6: 2175-2181.
42. 　Bartling B, Hofmann HS, Sohst A, et al. Prognostic potential and tumor growth-inhibiting effect of plasma advanced glycation end products in non-small cell lung carcinoma [J]. Mol Med, 2011, 17(9-10): 980-989.
43. 　Krebs MG, Hou JM, Sloane R, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches[J]. J Thorac Oncol, 2012, 7(2): 306-315.
44. 　Hofman V, Ilie MI, Long E, et al. Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the Cell Search AssayTM and the isolation by size of epithelial tumor cell method [J]. Int J Cancer, 2011, 129(7): 1651-1660.
45. 　Ma XL, Xiao ZL, Liu L，et al. Meta-analysis of circulating tumor cells as a prognostic marker in lung cancer[J]. Asian Pac J Cancer Prev, 2012, 13(4): 1137-1144.
46. 　Devriese LA, Bosma AJ, van de Heuvel MM, et al. Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis[J]. Lung Cancer, 2012, 75(2): 242-247.
47. 　Kato H, Nishimura T, Hirano T, et al. A clinician view and experience of proteomic studies in the light of lung cancer in Japanese healthcare[J]. J Proteome Res, 2011, 10(1): 51-57.
48. 　Ostroff RM, Bigbee WL, Franklin W, et al. Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer [J]. PLoS One, 2010, 5(12): e15003.
49. 　Cremona M, Calabrò E, Randi G, et al. Elevated levels of the acute-phase serum amyloid are associated with heightened lung cancer risk [J]. Cancer, 2010, 116(5): 1326-1335.
50. 　张恒, 陈胜喜, 黄凌瑾, 等. 非小细胞肺癌血清标志物PACAP的蛋白质组学筛选和鉴定[J]. 中国肺癌杂志, 2012, 15(5): 287-293.
51. 　Yang J, Song YC, Song TS, et al. Identification of novel low molecular weight serum peptidome biomarkers for non-small cell lung cancer (NSCLC) [J]. J Clin Lab Anal, 2012, 26(3): 148-154.
52. 　Du J, Yang SY, Lin XL, et al. Biomarker discovery and identification from non-small cell lung cancer sera[J]. Front Biosci (Elite Ed), 2011, 3: 1-10.
53. 　Patz EF Jr, Campa MJ, Gottlin EB, et al. Panel of serum biomarkers for the diagnosis of lung cancer [J]. J Clin Oncol, 2007, 25(35): 5578-5583.
54. 　Sreseli RT, Binder H, Kuhn M, et al. Identification of a 17-protein signature in the serum of lung cancer patients[J]. Oncol Rep, 2010, 24(1): 263-270.
55. 　Kumar S, Guleria R, Singh V, et al. Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy[J]. Lung cancer, 2010, 70(2): 211-217.
56. 　Paci M, Maramotti S, Bellesia E, et al. Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer[J]. Lung cancer, 2009, 64(1): 92-97.
57. 　Begum S, Brait M, Dasgupta S, et al. An epigenetic marker panel for detection of lung cancer using cell-free serum DNA [J]. Clin Cancer Res, 2011, 17(13): 4494-503.
58. 　Ulivi P, Zoli W, Calistri D, et al. p16INK4A and CDH13 hypermethylation in tumor and serum of non-small celllung cancer patients [J]. J Cell Physiol, 2006, 206(3): 611-615.
59. 　刘晋祎, 安倩, 许冠东, 等. 肺癌患者外周血血浆中p16基因异常甲基化的检测[J]. 中国肿瘤杂志, 2004, 26(3): 154-157.
60. 　Tsao DA, Yang MJ, Chang HJ, et al. A fast and convenient new technique to detect the therapeutic target, K-ras mutant, from peripheral blood in non-small cell lung cancer patients [J]. Lung Cancer, 2010, 68(1): 51-57.
61. 　Ramirez JL, Sarries C, de Castro PL, et al. Methylation patterns and K-ras mutations in tumor and paired serum of resected non-small cell lung cancer patients [J]. Cancer Lett, 2003, 193(2): 207-216.
62. 　Beau-Faller M, Gaub MP, Schneider A, et al. Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer Patients[J]. Int J Cancer, 2003, 105(3): 361-370.
63. 　Sozzi G, Musso K, Ratcliffe C, et al. Detection of microsatellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis [J]. Clin Cancer Res, 1999, 5(10): 2689-2692.
64. 　Vinayanuwattikun C, Sriuranpong V, Tanasanvimon S, et al. Epithelial-specific methylation marker: a potential plasma biomarker in advanced non-small cell lung cancer[J]. J Thorac Oncol, 2011, 6(11): 1818-1825.
65. 　Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath[J]. BMC Cancer, 2009, 9(1): 348.
66. 　Ligor M, Ligor T, Bajtarevic A, et al. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry [J]. Clin Chem LabMed, 2009, 47(5): 550-560.
67. 　Fuchs P, Loeseken C, Schubert JK, et al. Breath gas aldehydes as biomarkers of lung cancer [J]. Int J Cancer, 2010, 126(11): 2663-2670.
68. 　Skeldon KD, McMillan LC, Wyse CA, et al. Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer [J]. Res Med, 2006, 100(2): 300-306.
69. 　刘虎, 宋耕, 秦涛, 等. 非小细胞肺癌患者呼气中挥发性有机化合物的定量分析[J]. 中华肿瘤防治杂志, 2009, 16(23): 1857-1859.
70. 　Han W, Wang T, Reilly AA, et al. Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients [J]. Respir Res, 2009, 10(1): 86.
71. 　Carpagnano GE, Foschino-Barbaro MP, Mulé G, et al. 3p micro satellite alterations in exhaled breath condensate from patients with non-small cell lung cancer [J]. Am J Respir Crit Care Med, 2005, 172(6): 738-744.
72. 　Carpagnano GE, Foschino-Barbaro MP, Spanevello A, et al. 3p microsatellite signature in exhaled breath condensate and tumor tissue of patients with lung cancer [J]. Am J Respir Crit Care Med, 2008, 177(3): 337-341.
73. 　Carpagnano GE, Spanevello A, Carpagnano F, et al. Prognostic value of exhaled microsatellite alterations at 3p in NSCLC patients[J]. Lung Cancer, 2009, 64(3): 334-340.
74. 　Jungraithmayr W, Frings C, Zissel G, et al. Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma[J]. Respirology, 2008, 13(7): 1022-1027.
75. 　陈金亮, 陈建荣, 陶一江, 等. 慢性阻塞性肺疾病患者呼出气冷凝液中白细胞三烯B4和肿瘤坏死因子-α的检测及其临床意义[J]. 中国危重病急救医学, 2008, 20(6): 357-360.
76. 　Barta I, Kullmann T, Csiszer E, et al. Analysis of cytokine pattern in exhaled breath condensate of patients with squamous cell lung carcinoma [J]. Int J Biol Markers, 2010, 25(1): 52-56.
77. 　Gessner C, Rechner B, Hammerschmidt S, et al. Angiogenic markers in breath condensate identify non-small cell lung cancer[J]. Lung Cancer, 2010, 68(2): 177-184.
78. 　Carpagnano GE, Spanevello A, Curci C, et al. IL-2, TNF-alpha, and leptin: local versus systemic concentrations in NSCLC patients[J]. Oncol Res, 2007, 16(8): 375-381.
79. 　Carpagnano GE, Spanevello A, Palladino GP, et al. Cigarette smoke and increased COX-2 and survivin levels in exhaled breath condensate of lung cancer patients: how hot is the link?[J]. Lung Cancer, 2010, 67(1): 108-113.
80. 　Barash O, Peled N, Hirsch FR, et al. Sniffing the unique “odor print” of non-small-cell lung cancer with gold nanoparticles[J]. Small, 2009, 5(22): 2618-2624.
81. 　Jiang F, Todd NW, Li R, et al. A panel of sputum-based genomic marker for early detection of lung cancer [J]. Cancer Prev Res, 2010, 3(12):1571-1578.
82. 　Jiang F, Todd NW, Qiu Q, et al. Combined genetic analysis of sputum and computed tomography for noninvasive diagnosis of non-small-cell lung cancer [J]. Lung Cancer, 2009, 66(1): 58-63.
83. 　Dimakou K, Hillas G, Bakakos P. Adenosine deaminase activity and its isoenzymes in the sputum of patients with pulmonary tuberculosis[J]. Int J Tuberc Lung Dis, 2009, 13(6): 744-748.
84. 　Yu L, Todd NW, Xing L, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers [J]. Int J Cancer, 2010, 127(12): 2870-2878.
85. 　李红梅, 付军桦, 修元德. 端粒酶与CYFRA21-1联合测定对肺癌所致恶性胸腔积液同良性胸腔积液鉴别的诊断意义[J]. 中国肺癌杂志, 2010, 13(6): 652-654.
86. 　Xing L, Todd NW, Yu L, et al. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers [J]. Mod Pathol, 2010, 23(8): 1157-1164.
87. 　Hsu HS, Chen TP, Wen CK, et al. Multiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessment[J]. J Pathol, 2007, 213(4): 412-419.
88. 　Hillas G, Moschos C, Dimakou K, et al. Carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 (CYFRA 21-1) levels in induced sputum of lung cancer patients[J]. Scand J Clin Lab Invest, 2008, 68(7): 542-547.
89. 　Pio R, Garcia J, Corrales L, et al. Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from patients with lung cancer[J]. Cancer Epidemiol, Biomarkers Prev, 2010, 19(10): 2665-2672.

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