肺癌自身抗体在肿瘤早期诊断和治疗中的临床应用进展
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摘要
肺癌是癌症相关性死亡的主要原因之一,对人群健康和生命具有极大的威胁。根据相关资料及统计学模型估计,在2012年全球约有1.41千万新发癌症病例,其中肺癌发病率为180万,占癌症发病率的13%,是癌症中诊断率最高的病种,也是全球男性、发达国家女性癌症死亡率最高的病种,在发展中国家女性死亡率仅次于乳腺癌。不同于西方发达国家,中国肺癌发病率从20世纪80年代初期开始一直呈现上升趋势,而西方工业发达国家自20世纪末期开始肺癌发病率便呈下降趋势或维持相对稳定的水平,而目前的检测手段对肺癌早期筛查的灵敏度、特异性不够,肺癌患者确诊时往往已经达到肺癌中晚期,使得肺癌的死亡率居高不下。近年来研究发现由肺癌自身抗原产生的相关抗体——肿瘤自身抗体对于肺癌的早期诊断和治疗有重大意义。我们针对自身抗体进行综述,以便于使得此技术能够更好地为临床利用。
Lung cancer is one of the leading causes of cancer-related death and poses a great threat to the health and life of the general population. According to relevant data and statistical models,there are about 1.41 million new cases of cancer over the world in 2012,including 1.8 million lung cancers,accounting for 13% of cancer incidence,which is the highest diagnosis rate among different cancer types. Meanwhile,it also has the highest cancer mortality rate among males and developed countries worldwide. The mortality rate of lung cancer in females in developing countries is on the second place,only lower than breast cancer. Unlike western developed countries,the incidence of lung cancer in China has been rising since the early 1980s, while in the western industrialized countries,the incidence of lung cancer has declined or remained relatively stable since the end of the 20 th century. The current detection methods have insufficient sensitivity and specificity for the early screening of lung cancer. Lung cancer mortality is maintained high due to its reaching the advanced lung cancer stage when diagnosed most of the time. In recent years, studies have found that antibodies against autoantigens of lung cancer, suggesting tumor autoantibodies have great significance for the early diagnosis and treatment of lung cancer. We have reviewed the autoantibodies in order to make this technology better for the clinical use.
Lung cancer is one of the leading causes of cancer-related death and poses a great threat to the health and life of the general population. According to relevant data and statistical models,there are about 1.41 million new cases of cancer over the world in 2012,including 1.8 million lung cancers,accounting for 13% of cancer incidence,which is the highest diagnosis rate among different cancer types. Meanwhile,it also has the highest cancer mortality rate among males and developed countries worldwide. The mortality rate of lung cancer in females in developing countries is on the second place,only lower than breast cancer. Unlike western developed countries,the incidence of lung cancer in China has been rising since the early 1980s, while in the western industrialized countries,the incidence of lung cancer has declined or remained relatively stable since the end of the 20 th century. The current detection methods have insufficient sensitivity and specificity for the early screening of lung cancer. Lung cancer mortality is maintained high due to its reaching the advanced lung cancer stage when diagnosed most of the time. In recent years, studies have found that antibodies against autoantigens of lung cancer, suggesting tumor autoantibodies have great significance for the early diagnosis and treatment of lung cancer. We have reviewed the autoantibodies in order to make this technology better for the clinical use.
引文
[1]TORRE L A,BRAY F,SIEGEL R L,et al. Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[2]CHEN W Q,ZHENG R S,PETER D B,et al. Cancer statistics in China 2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]韦春晖.早期肺癌诊断进展[J].临床肺科杂志,2010,15(8):1136-1138.
[4]SIEGEL R, NAISHADHAM D, JEMAL A. Cancer statistics,2012[J].CA Cancer J Clin,2012,62(1):10-29.
[5]BAYKUL T, YILMAZ H H,AYDIN U,et al. Early diagnosis of oral cancer[J]. J Int Med Res,2010,38(3):737-749.
[6]KAUR S,BAINE M J,JAIN M,et al. Early diagnosis of pancreatic cancer:challenges and new developments[J]. Biomark Med,2012,6(5):597-612.
[7]JEMAL A,CLEGG LX,WARD E,et al. Annual report to the nation on the status of cancer, 1975-2001,with a special feature regarding survival[J]. Cancer,2004,101(1):3-27.
[8]YAO X,JIANG H,ZHANG C,et al. Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung cancer[J].Biomarkers,2010,15(2):128-134.
[9]ZHANG Y,YING X,HAN S,et al. Autoantibodies against insulinlike growth factorbinding protein-2 as a serological biomarker in the diagnosis of lung cancer[J]. Int J Oncol,2013,42(1):93-100.
[10]ZHONG L,COE S P, STROMBERG A J, et al. Profiling tumorassociated antibodies for early detection of non-small cell lung cancer[J]. J Thorac Oncol,2006,1(6):513-519.
[11]TAN E M. Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis[J]. J Clin Invest, 2001,108(10):1411-1415.
[12]PEREIRA-FACA S R,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.
[13]TAN H T, LOW J, LIM S G, et al. Serum autoantibodiesas biomarkers forearly cancer detection[J]. FEBS J,2009,276(23):6880-6904.
[14]FITZPATRICK D R,GERMAIN-LEE E, VALLE D. Isolation and characterization of rat and human cDNAs encoding a novel putative peroxisomal enoyl-CoA hydratase[J]. Genomics, 1995,27(3):457-66.
[15]DAI L,LI J, TSAY J J, et al. Identification of autoantibodies toECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer[J]. Oncoimmunology, 2017, 6(5):e1310359.
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[17]GAUTIER F, IRMINGER-FINGER I, GREGOIRE M, et al.Identification of an apoptotic cleavage product of BARD 1 as an autoantigen:a potential factor in the antitumoral response mediated by apoptotic bodies[J]. Cancer Res,2000,60(24):6895-6900.
[18]IRMINGER-FINGER I, RATAJSKA M, PILYUGIN M. New concepts on BARD1:Regulator of BRCA pathways and beyond[J].Int J Biochem Cell Biol,2015,72:1-17.
[19]IRMINGER-FINGER I,JEFFORD C E. Is there more to BARD1than BRCAl[J]? Nat Rev Cancer,2006,6(5):382-391.
[20]BAER R,LUDWIG T. The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity[J]. Curr Opin Genet Dev,2002,12(1):86-91.
[21]FEKI A, JEFFORD C E, BERARDI P, et al. BARDl induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase[J]. Oncogene,2005,24(23):3726-3736.
[22]IRMINGER-FINGER I,LEUNG W C,LI J,et al. Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis[J]. Mol Cell,2001,8(6):1255-1266.
[23]JEFFORD C E, FEKI A, HARB J, et al. Nuclear-cytoplasmic translocation of BARDl is linked to its apoptotic activity[J].Oncogene,2004,23(20):3509-3520.
[24]BOSSE K R,DISKIN S J,COLE K A,et al. Common variation at BARD1 results in the expressionof an oncogenic isoform that influences neuroblastoma susceptibility and oncogenicity[J]. Cancer Res,2012,72(8):2068-2078.
[25]LI L,RYSER S, DIZIN E, et al. Oncogenic BARD1 isoforms expressed in gynecological cancers[J]. Cancer Res,2007,67(24):11876-11885.
[26]OZDEN O,BISHEHSARI F, BAUER J, et al. Expression of an oncogenic BARDI Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 inhibitor therapy in colon cancer[J]. Sci Rep,2016,6:26273.
[27]SPORN J C,HOTHORN T,JUNG B H. BARDI expression predicts outcome in colon cancer[J]. Clin Cancer Res,2011,17(16):5451-5462.
[28]WU J Y,VLASTOS A T,PELTE M F,et al. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis[J]. Int J Cancer,2006,118(5):1215-1226.
[29]ZHANG Y Q, BIANCO A, MALKINSON A M, et al. BARDl:an independent predictor of survival in non-small cell lung cancer[J].Int J Cancer,2012,131(1):83-94.
[30]ZHANG Y Q, PILYUGIN M, KUESTER D, et al. Expression of oncogenic BARDl isoforms affects colon cancer progression and correlates with clinical outcome[J]. Br J Cancer,2012,107(4):675-683.
[31]RYSER S,DIZIN E,JEFFORD C E,et al. Distinct roles of BARD1isoforms in mitosis:full-length BARD1 mediates Aurora B degradation, cancer-associated BARDlbeta scaffolds Aurora B and BRCA2[J]. Cancer Res,2009,69(3):1125-1134.
[32]PILYUGIN M, ANDRE P A, RATAJSKA M, et al. Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δin telomere stability[J]. Oncotarget,2017,8(6):9339-9353.
[33]SMITH G P. Filamentous fusion phage:novel expression vectors that display cloned antigens on the virion surface[J]. Science,1985,228(4705):1315-1317.
[34]DANNER S,BELASCO J G. T7 phage display:a novel genetic selection system for cloning RNA-binding proteins from cDNA libraries[J]. Proc Natl Acad Sci USA, 2001,98(23):12954-12959.
[35]WU L, CHANG W, ZHAO J, et al. Development of autoantibody signature s as novel diagnostic biomarkers of non-small cell lung cancer[J]. Clin Cancer Res,2010,16(14):3760-3768.
[36]KOZIOL J A, ZHANG J Y, CASIANO C A, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis[J]. Clin Cancer Res,2003,9(14):5120-5126.
[37]CHAPMAN C J, MURRAY A, McELVEEN J E, et al.Autoantibodies in lung cancer:possibilities for early detection and subsequent cure[J]. Thorax,2008,63(3):228-233.
[38]FARLOW E C, PATEL K, BASU S, et al. Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of non-small cell lung cancer[J]. Clin Cancer Res,2010,16(13):3452-3462.
[39]KIJANKA G, MURPHY D. Protein arrays as tools for serum autoantibody marker discovery in cancer[J]. J Proteomics,2009,72(6):936-944.
[40]SARTAIN M J,SLAYDEN R A, SINGH K K, et al. Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling[J]. Mol Cell Proteomics, 2006, 5(11):2102-2113.
[41]SHAN Q,LOU X,XIAO T,et al. A cancer/testis antigen microarray to screen autoantibody biomarkers of non-small cell lung cancer[J]. Cancer Lett,2013,328(1):160-167.
[42]TANG Z M,LING Z G. Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer:A systematic review and metaanalysis[J].PLoS One,2017,12(7):e0182117.
[43]YAO Y,FAN Y,WU J,et al. Potential application of non-small cell lung cancer-associated autoantibodies to early cancer diagnosis[J].Biochem Biophys Res Commun,2012,423(3):613-619.
[44]OKANO T,SEIKE M, KURIBAYASHI H, et al. Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling[J]. Int J Oncol,2016,48(3):945-952.
[45]BUSHEY RT, MOODY MA, NICELY N L, et al. et al. A Therapeutic antibody for cancer, derived from single human B cells[J]. Cell Rep,2016,15(7):1505-1513.
[2]CHEN W Q,ZHENG R S,PETER D B,et al. Cancer statistics in China 2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]韦春晖.早期肺癌诊断进展[J].临床肺科杂志,2010,15(8):1136-1138.
[4]SIEGEL R, NAISHADHAM D, JEMAL A. Cancer statistics,2012[J].CA Cancer J Clin,2012,62(1):10-29.
[5]BAYKUL T, YILMAZ H H,AYDIN U,et al. Early diagnosis of oral cancer[J]. J Int Med Res,2010,38(3):737-749.
[6]KAUR S,BAINE M J,JAIN M,et al. Early diagnosis of pancreatic cancer:challenges and new developments[J]. Biomark Med,2012,6(5):597-612.
[7]JEMAL A,CLEGG LX,WARD E,et al. Annual report to the nation on the status of cancer, 1975-2001,with a special feature regarding survival[J]. Cancer,2004,101(1):3-27.
[8]YAO X,JIANG H,ZHANG C,et al. Dickkopf-1 autoantibody is a novel serological biomarker for non-small cell lung cancer[J].Biomarkers,2010,15(2):128-134.
[9]ZHANG Y,YING X,HAN S,et al. Autoantibodies against insulinlike growth factorbinding protein-2 as a serological biomarker in the diagnosis of lung cancer[J]. Int J Oncol,2013,42(1):93-100.
[10]ZHONG L,COE S P, STROMBERG A J, et al. Profiling tumorassociated antibodies for early detection of non-small cell lung cancer[J]. J Thorac Oncol,2006,1(6):513-519.
[11]TAN E M. Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis[J]. J Clin Invest, 2001,108(10):1411-1415.
[12]PEREIRA-FACA S R,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.
[13]TAN H T, LOW J, LIM S G, et al. Serum autoantibodiesas biomarkers forearly cancer detection[J]. FEBS J,2009,276(23):6880-6904.
[14]FITZPATRICK D R,GERMAIN-LEE E, VALLE D. Isolation and characterization of rat and human cDNAs encoding a novel putative peroxisomal enoyl-CoA hydratase[J]. Genomics, 1995,27(3):457-66.
[15]DAI L,LI J, TSAY J J, et al. Identification of autoantibodies toECH1 and HNRNPA2B1 as potential biomarkers in the early detection of lung cancer[J]. Oncoimmunology, 2017, 6(5):e1310359.
[16]BIAMONTI G,RUGGIU M,SACCONE S,et al, Two homologous genes,originated by duplication, encode the human hnRNP proteins A2 and Al[J]. Nucleic Acids Res, 1994,22(11):1996-2002.
[17]GAUTIER F, IRMINGER-FINGER I, GREGOIRE M, et al.Identification of an apoptotic cleavage product of BARD 1 as an autoantigen:a potential factor in the antitumoral response mediated by apoptotic bodies[J]. Cancer Res,2000,60(24):6895-6900.
[18]IRMINGER-FINGER I, RATAJSKA M, PILYUGIN M. New concepts on BARD1:Regulator of BRCA pathways and beyond[J].Int J Biochem Cell Biol,2015,72:1-17.
[19]IRMINGER-FINGER I,JEFFORD C E. Is there more to BARD1than BRCAl[J]? Nat Rev Cancer,2006,6(5):382-391.
[20]BAER R,LUDWIG T. The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity[J]. Curr Opin Genet Dev,2002,12(1):86-91.
[21]FEKI A, JEFFORD C E, BERARDI P, et al. BARDl induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase[J]. Oncogene,2005,24(23):3726-3736.
[22]IRMINGER-FINGER I,LEUNG W C,LI J,et al. Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis[J]. Mol Cell,2001,8(6):1255-1266.
[23]JEFFORD C E, FEKI A, HARB J, et al. Nuclear-cytoplasmic translocation of BARDl is linked to its apoptotic activity[J].Oncogene,2004,23(20):3509-3520.
[24]BOSSE K R,DISKIN S J,COLE K A,et al. Common variation at BARD1 results in the expressionof an oncogenic isoform that influences neuroblastoma susceptibility and oncogenicity[J]. Cancer Res,2012,72(8):2068-2078.
[25]LI L,RYSER S, DIZIN E, et al. Oncogenic BARD1 isoforms expressed in gynecological cancers[J]. Cancer Res,2007,67(24):11876-11885.
[26]OZDEN O,BISHEHSARI F, BAUER J, et al. Expression of an oncogenic BARDI Splice Variant Impairs Homologous Recombination and Predicts Response to PARP-1 inhibitor therapy in colon cancer[J]. Sci Rep,2016,6:26273.
[27]SPORN J C,HOTHORN T,JUNG B H. BARDI expression predicts outcome in colon cancer[J]. Clin Cancer Res,2011,17(16):5451-5462.
[28]WU J Y,VLASTOS A T,PELTE M F,et al. Aberrant expression of BARD1 in breast and ovarian cancers with poor prognosis[J]. Int J Cancer,2006,118(5):1215-1226.
[29]ZHANG Y Q, BIANCO A, MALKINSON A M, et al. BARDl:an independent predictor of survival in non-small cell lung cancer[J].Int J Cancer,2012,131(1):83-94.
[30]ZHANG Y Q, PILYUGIN M, KUESTER D, et al. Expression of oncogenic BARDl isoforms affects colon cancer progression and correlates with clinical outcome[J]. Br J Cancer,2012,107(4):675-683.
[31]RYSER S,DIZIN E,JEFFORD C E,et al. Distinct roles of BARD1isoforms in mitosis:full-length BARD1 mediates Aurora B degradation, cancer-associated BARDlbeta scaffolds Aurora B and BRCA2[J]. Cancer Res,2009,69(3):1125-1134.
[32]PILYUGIN M, ANDRE P A, RATAJSKA M, et al. Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δin telomere stability[J]. Oncotarget,2017,8(6):9339-9353.
[33]SMITH G P. Filamentous fusion phage:novel expression vectors that display cloned antigens on the virion surface[J]. Science,1985,228(4705):1315-1317.
[34]DANNER S,BELASCO J G. T7 phage display:a novel genetic selection system for cloning RNA-binding proteins from cDNA libraries[J]. Proc Natl Acad Sci USA, 2001,98(23):12954-12959.
[35]WU L, CHANG W, ZHAO J, et al. Development of autoantibody signature s as novel diagnostic biomarkers of non-small cell lung cancer[J]. Clin Cancer Res,2010,16(14):3760-3768.
[36]KOZIOL J A, ZHANG J Y, CASIANO C A, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis[J]. Clin Cancer Res,2003,9(14):5120-5126.
[37]CHAPMAN C J, MURRAY A, McELVEEN J E, et al.Autoantibodies in lung cancer:possibilities for early detection and subsequent cure[J]. Thorax,2008,63(3):228-233.
[38]FARLOW E C, PATEL K, BASU S, et al. Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of non-small cell lung cancer[J]. Clin Cancer Res,2010,16(13):3452-3462.
[39]KIJANKA G, MURPHY D. Protein arrays as tools for serum autoantibody marker discovery in cancer[J]. J Proteomics,2009,72(6):936-944.
[40]SARTAIN M J,SLAYDEN R A, SINGH K K, et al. Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling[J]. Mol Cell Proteomics, 2006, 5(11):2102-2113.
[41]SHAN Q,LOU X,XIAO T,et al. A cancer/testis antigen microarray to screen autoantibody biomarkers of non-small cell lung cancer[J]. Cancer Lett,2013,328(1):160-167.
[42]TANG Z M,LING Z G. Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer:A systematic review and metaanalysis[J].PLoS One,2017,12(7):e0182117.
[43]YAO Y,FAN Y,WU J,et al. Potential application of non-small cell lung cancer-associated autoantibodies to early cancer diagnosis[J].Biochem Biophys Res Commun,2012,423(3):613-619.
[44]OKANO T,SEIKE M, KURIBAYASHI H, et al. Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling[J]. Int J Oncol,2016,48(3):945-952.
[45]BUSHEY RT, MOODY MA, NICELY N L, et al. et al. A Therapeutic antibody for cancer, derived from single human B cells[J]. Cell Rep,2016,15(7):1505-1513.
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