All Title Author
Keywords Abstract

PLOS ONE  2012 

Integrative Proteomics and Tissue Microarray Profiling Indicate the Association between Overexpressed Serum Proteins and Non-Small Cell Lung Cancer

DOI: 10.1371/journal.pone.0051748

Full-Text   Cite this paper   Add to My Lib

Abstract:

Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC) can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA) and Multiple reaction monitoring (MRM) assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG) and Leucine-rich alpha-2-glycoprotein (LRG1), two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.

References

[1]  Jemal A, Siegel R, Ward E, Hao Y, Xu J, et al. (2009) Cancer statistics, 2009. CA Cancer J Clin 59: 225–249.
[2]  O'Byrne KJ, Danson S, Dunlop D, Botwood N, Taguchi F, et al. (2007) Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non small-cell lung cancer. J Clin Oncol 25: 3266–3273.
[3]  Kassis ES, Vaporciyan AA, Swisher SG, Correa AM, Bekele BN, et al. (2009) Application of the revised lung cancer staging system (IASLC Staging Project) to a cancer center population. J Thorac Cardiovasc Surg 138: 412–412, 412-418, e411-412.
[4]  Bharti A, Ma PC, Salgia R (2007) Biomarker discovery in lung cancer–promises and challenges of clinical proteomics. Mass Spectrom Rev 26: 451–466.
[5]  Nedelkov D, Kiernan UA, Niederkofler EE, Tubbs KA, Nelson RW (2005) Investigating diversity in human plasma proteins. Proc Natl Acad Sci U S A 102: 10852–10857.
[6]  Lee HJ, Lee EY, Kwon MS, Paik YK (2006) Biomarker discovery from the plasma proteome using multidimensional fractionation proteomics. Curr Opin Chem Biol 10: 42–49.
[7]  Dai J, Shieh CH, Sheng QH, Zhou H, Zeng R (2005) Proteomic analysis with integrated multiple dimensional liquid chromatography/mass spectrometry based on elution of ion exchange column using pH steps. Anal Chem 77: 5793–5799.
[8]  DeSouza L, Diehl G, Rodrigues MJ, Guo J, Romaschin AD, et al. (2005) Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. J Proteome Res 4: 377–386.
[9]  Faca V, Coram M, Phanstiel D, Glukhova V, Zhang Q, et al. (2006) Quantitative analysis of acrylamide labeled serum proteins by LC-MS/MS. J Proteome Res 5: 2009–2018.
[10]  Huttenhain R, Malmstrom J, Picotti P, Aebersold R (2009) Perspectives of targeted mass spectrometry for protein biomarker verification. Curr Opin Chem Biol 13: 518–525.
[11]  Colantonio DA, Dunkinson C, Bovenkamp DE, Van Eyk JE (2005) Effective removal of albumin from serum. Proteomics 5: 3831–3835.
[12]  Fu Q, Garnham CP, Elliott ST, Bovenkamp DE, Van Eyk JE (2005) A robust, streamlined, and reproducible method for proteomic analysis of serum by delipidation, albumin and IgG depletion, and two-dimensional gel electrophoresis. Proteomics 5: 2656–2664.
[13]  Liu Y, Li C, Xing Z, Yuan X, Wu Y, et al. (2010) Proteomic mining in the dysplastic liver of WHV/c-myc mice–insights and indicators for early hepatocarcinogenesis. FEBS J 277: 4039–4053.
[14]  Elias JE, Gygi SP (2007) Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods 4: 207–214.
[15]  Sheng Q, Dai J, Wu Y, Tang H, Zeng R (2012) BuildSummary: Using group-based approach to improve the sensitivity of peptide/protein identification in shotgun proteomics. J Proteome Res 11: 1494–1502.
[16]  Reiter L, Claassen M, Schrimpf SP, Jovanovic M, Schmidt A, et al. (2009) Protein identification false discovery rates for very large proteomics data sets generated by tandem mass spectrometry. Mol Cell Proteomics 8: 2405–2417.
[17]  Luo X, Liu Y, Wang R, Hu H, Zeng R, et al. (2011) A high-quality secretome of A549 cells aided the discovery of C4b-binding protein as a novel serum biomarker for non-small cell lung cancer. J Proteomics 74: 528–538.
[18]  Rikova K, Guo A, Zeng Q, Possemato A, Yu J, et al. (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131: 1190–1203.
[19]  Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, et al. (2003) GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 4: R28.
[20]  Morrissey ER, Diaz-Uriarte R (2009) Pomelo II: finding differentially expressed genes. Nucleic Acids Res 37: W581–586.
[21]  Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, et al. (2011) pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12: 77.
[22]  Taylor IW, Linding R, Warde-Farley D, Liu Y, Pesquita C, et al. (2009) Dynamic modularity in protein interaction networks predicts breast cancer outcome. Nat Biotechnol 27: 199–204.
[23]  Kuzyk MA, Smith D, Yang J, Cross TJ, Jackson AM, et al. (2009) Multiple reaction monitoring-based, multiplexed, absolute quantitation of 45 proteins in human plasma. Mol Cell Proteomics 8: 1860–1877.
[24]  Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA (2007) Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 6: 2212–2229.
[25]  States DJ, Omenn GS, Blackwell TW, Fermin D, Eng J, et al. (2006) Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study. Nat Biotechnol 24: 333–338.
[26]  Nesvizhskii AI, Keller A, Kolker E, Aebersold R (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75: 4646–4658.
[27]  Polanski M, Anderson NL (2007) A list of candidate cancer biomarkers for targeted proteomics. Biomark Insights 1: 1–48.
[28]  Anderson L (2005) Candidate-based proteomics in the search for biomarkers of cardiovascular disease. J Physiol 563: 23–60.
[29]  Dowling P, O'Driscoll L, Meleady P, Henry M, Roy S, et al. (2007) 2-D difference gel electrophoresis of the lung squamous cell carcinoma versus normal sera demonstrates consistent alterations in the levels of ten specific proteins. Electrophoresis 28: 4302–4310.
[30]  Chatterji B, Borlak J (2007) Serum proteomics of lung adenocarcinomas induced by targeted overexpression of c-raf in alveolar epithelium identifies candidate biomarkers. Proteomics 7: 3980–3991.
[31]  Chatterji B, Borlak J (2009) A 2-DE MALDI-TOF study to identify disease regulated serum proteins in lung cancer of c-myc transgenic mice. Proteomics 9: 1044–1056.
[32]  Okano T, Kondo T, Kakisaka T, Fujii K, Yamada M, et al. (2006) Plasma proteomics of lung cancer by a linkage of multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis. Proteomics 6: 3938–3948.
[33]  Hanash SM, Pitteri SJ, Faca VM (2008) Mining the plasma proteome for cancer biomarkers. Nature 452: 571–579.
[34]  Hong Q, Sze CI, Lin SR, Lee MH, He RY, et al. (2009) Complement C1q activates tumor suppressor WWOX to induce apoptosis in prostate cancer cells. PLoS One 4: e5755.
[35]  Cheng AJ, Chen LC, Chien KY, Chen YJ, Chang JT, et al. (2005) Oral cancer plasma tumor marker identified with bead-based affinity-fractionated proteomic technology. Clin Chem 51: 2236–2244.
[36]  Zhu WL, Fan BL, Liu DL, Zhu WX (2009) Abnormal expression of fibrinogen gamma (FGG) and plasma level of fibrinogen in patients with hepatocellular carcinoma. Anticancer Res 29: 2531–2534.
[37]  Pan S, Cheng L, White JT, Lu W, Utleg AG, et al. (2009) Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers. OMICS 13: 345–354.
[38]  Fiedler GM, Leichtle AB, Kase J, Baumann S, Ceglarek U, et al. (2009) Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer. Clin Cancer Res 15: 3812–3819.
[39]  Badve SS, Baehner FL, Gray RP, Childs BH, Maddala T, et al. (2008) Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol 26: 2473–2481.
[40]  Goncalves A, Charafe-Jauffret E, Bertucci F, Audebert S, Toiron Y, et al. (2008) Protein profiling of human breast tumor cells identifies novel biomarkers associated with molecular subtypes. Mol Cell Proteomics 7: 1420–1433.
[41]  Hebbar V, Damera G, Sachdev GP (2005) Differential expression of MUC genes in endometrial and cervical tissues and tumors. BMC Cancer 5: 124.
[42]  Li C, Chen Z, Xiao Z, Wu X, Zhan X, et al. (2003) Comparative proteomics analysis of human lung squamous carcinoma. Biochem Biophys Res Commun 309: 253–260.
[43]  Li C, Xiao Z, Chen Z, Zhang X, Li J, et al. (2006) Proteome analysis of human lung squamous carcinoma. Proteomics 6: 547–558.
[44]  Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RM, et al. (2005) The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol Cell 17: 331–339.
[45]  Nakagawa T, Otake Y, Yanagihara K, Miyahara R, Ishikawa S, et al. (2004) Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC). Lung Cancer 43: 145–149.
[46]  Tian M, Cui YZ, Song GH, Zong MJ, Zhou XY, et al. (2008) Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients. BMC Cancer 8: 241.
[47]  Kreunin P, Zhao J, Rosser C, Urquidi V, Lubman DM, et al. (2007) Bladder cancer associated glycoprotein signatures revealed by urinary proteomic profiling. J Proteome Res 6: 2631–2639.
[48]  Zeng Z, Hincapie M, Haab BB, Hanash S, Pitteri SJ, et al. (2010) The development of an integrated platform to identify breast cancer glycoproteome changes in human serum. J Chromatogr A 1217: 3307–3315.
[49]  Li C, Zolotarevsky E, Thompson I, Anderson MA, Simeone DM, et al. (2011) A multiplexed bead assay for profiling glycosylation patterns on serum protein biomarkers of pancreatic cancer. Electrophoresis 32: 2028–2035.
[50]  Weivoda S, Andersen JD, Skogen A, Schlievert PM, Fontana D, et al. (2008) ELISA for human serum leucine-rich alpha-2-glycoprotein-1 employing cytochrome c as the capturing ligand. J Immunol Methods 336: 22–29.
[51]  O'Donnell LC, Druhan LJ, Avalos BR (2002) Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation. J Leukoc Biol 72: 478–485.
[52]  Kawakami T, Hoshida Y, Kanai F, Tanaka Y, Tateishi K, et al. (2005) Proteomic analysis of sera from hepatocellular carcinoma patients after radiofrequency ablation treatment. Proteomics 5: 4287–4295.
[53]  Kakisaka T, Kondo T, Okano T, Fujii K, Honda K, et al. (2007) Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE): up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer. J Chromatogr B Analyt Technol Biomed Life Sci 852: 257–267.
[54]  Cummings C, Walder J, Treeful A, Jemmerson R (2006) Serum leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay. Apoptosis 11: 1121–1129.
[55]  Cima I, Schiess R, Wild P, Kaelin M, Schuffler P, et al. (2011) Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer. Proc Natl Acad Sci U S A 108: 3342–3347.
[56]  Patz EF Jr, Campa MJ, Gottlin EB, Kusmartseva I, Guan XR, et al. (2007) Panel of serum biomarkers for the diagnosis of lung cancer. J Clin Oncol 25: 5578–5583.
[57]  Ueda K, Katagiri T, Shimada T, Irie S, Sato TA, et al. (2007) Comparative profiling of serum glycoproteome by sequential purification of glycoproteins and 2-nitrobenzensulfenyl (NBS) stable isotope labeling: a new approach for the novel biomarker discovery for cancer. J Proteome Res 6: 3475–3483.
[58]  Heo SH, Lee SJ, Ryoo HM, Park JY, Cho JY (2007) Identification of putative serum glycoprotein biomarkers for human lung adenocarcinoma by multilectin affinity chromatography and LC-MS/MS. Proteomics 7: 4292–4302.
[59]  Howard BA, Wang MZ, Campa MJ, Corro C, Fitzgerald MC, et al. (2003) Identification and validation of a potential lung cancer serum biomarker detected by matrix-assisted laser desorption/ionization-time of flight spectra analysis. Proteomics 3: 1720–1724.
[60]  Maciel CM, Junqueira M, Paschoal ME, Kawamura MT, Duarte RL, et al. (2005) Differential proteomic serum pattern of low molecular weight proteins expressed by adenocarcinoma lung cancer patients. J Exp Ther Oncol 5: 31–38.
[61]  Fujii K, Nakano T, Kanazawa M, Akimoto S, Hirano T, et al. (2005) Clinical-scale high-throughput human plasma proteome analysis: lung adenocarcinoma. Proteomics 5: 1150–1159.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

微信:OALib Journal