Login Register Cart 0
Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Label-Free Mass Spectrometry-Based Plasma Proteomics Identified LY6D, DSC3, CDSN, SERPINB12, and SLURP1 as Novel Protein Biomarkers For Pulmonary Tuberculosis

Author(s): Lu Zhang, Hualin Wang, Na Li, Peng Hu, Zhaoqin Zhu, Wei Wang, Yanzheng Song, Zilu Wen, Xiaoli Yu* and Shulin Zhang*

Volume 18, Issue 1, 2021

Published on: 09 December, 2019

Page: [50 - 61] Pages: 12

DOI: 10.2174/1570164617666191210105122

Price: $65

Abstract

Aim: We aimed to identify new plasma biomarkers for the diagnosis of Pulmonary Tuberculosis (PTB).

Background: Tuberculosis is an ancient infectious disease that remains one of the major global health problems. Until now, effective, convenient, and affordable methods for diagnosis of PTB were still lacking.

Objective: This study focused on constructing a label-free LC-MS/MS-based comparative proteomics between six tuberculosis patients and six healthy controls to identify Differentially Expressed Proteins (DEPs) in plasma.

Methods: To reduce the influences of high-abundant proteins, albumin and globulin were removed from plasma samples using affinity gels. Then DEPs from the plasma samples were identified using a label-free Quadrupole-Orbitrap LC-MS/MS system. The results were analyzed by the protein database search algorithm SEQUEST-HT to identify mass spectra to peptides. The predictive abilities of combinations of host markers were investigated by General Discriminant Analysis (GDA), with Leave-One-Out Cross- Validation (LOOCV).

Results: A total of 572 proteins were identified and 549 proteins were quantified. The threshold for DEPs was set as adjusted p-value< 0.05 and fold change ≥1.5 or ≤0.6667, 32 DEPs were found. ClusterVis, TBtools, and STRING were used to find new potential biomarkers of PTB. Six proteins, LY6D, DSC3, CDSN, FABP5, SERPINB12, and SLURP1, which performed well in the LOOCV method validation, were termed as potential biomarkers. The percentage of cross-validated grouped cases correctly classified and original grouped cases correctly classified is greater than or equal to 91.7%.

Conclusion: We successfully identified five candidate biomarkers for immunodiagnosis of PTB in plasma, LY6D, DSC3, CDSN, SERPINB12, and SLURP1. Our work supported this group of proteins as potential biomarkers for PTB, and be worthy of further validation.

Keywords: Tuberculosis, plasma, label-free LC-MS/MS, biomarkers, diagnose, proteomics.

« Previous Next »
Graphical Abstract

[1]
Global, H.; Tuberculo, T.O.E.N.D. Global Report Tuberculosis, 2018, 2018, 12.
[2]
Chegou, N.N.; Hoek, K.G.; Kriel, M.; Warren, R.M.; Victor, T.C.; Walzl, G. Tuberculosis assays: Past, present and future. Expert Rev. Anti Infect. Ther., 2011, 9(4), 457-469.
[http://dx.doi.org/10.1586/eri.11.23] [PMID: 21504402]
[3]
Chisti, M.J.; Graham, S.M.; Duke, T.; Ahmed, T.; Ashraf, H.; Faruque, A.S.G.; La Vincente, S.; Banu, S.; Raqib, R.; Salam, M.A. A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay. PLoS One, 2014, 9(4)e93776
[http://dx.doi.org/10.1371/journal.pone.0093776] [PMID: 24695758]
[4]
Wang, J.; Zhu, X.; Xiong, X.; Ge, P.; Liu, H.; Ren, N.; Khan, F.A.; Zhou, X.; Zhang, L.; Yuan, X.; Chen, X.; Chen, Y.; Hu, C.; Robertson, I.D.; Chen, H.; Guo, A. Identification of potential urine proteins and microRNA biomarkers for the diagnosis of pulmonary tuberculosis patients. Emerg. Microbes Infect., 2018, 7(1), 63.
[http://dx.doi.org/10.1038/s41426-018-0066-5] [PMID: 29636444]
[5]
Adilakshmi, T.; Laine, R.O. Ribosomal protein S25 mRNA partners with MTF-1 and La to provide a p53-mediated mechanism for survival or death. J. Biol. Chem., 2002, 277(6), 4147-4151.
[http://dx.doi.org/10.1074/jbc.M109785200] [PMID: 11741912]
[6]
Fischer, T.; Elenko, E.; McCaffery, J.M.; DeVries, L.; Farquhar, M.G. Clathrin-coated vesicles bearing GAIP possess GTPase-activating protein activity in vitro. Proc. Natl. Acad. Sci. USA, 1999, 96(12), 6722-6727.
[http://dx.doi.org/10.1073/pnas.96.12.6722] [PMID: 10359779]
[7]
Prozialeck, W.C.; Fay, M.J.; Lamar, P.C.; Pearson, C.A.; Sigar, I.; Ramsey, K.H. Chlamydia trachomatis disrupts N-cadherin-dependent cell-cell junctions and sequesters β-catenin in human cervical epithelial cells. Infect. Immun., 2002, 70(5), 2605-2613.
[http://dx.doi.org/10.1128/IAI.70.5.2605-2613.2002] [PMID: 11953402]
[8]
Roberts, K.P.; Ensrud, K.M.; Hamilton, D.W. A comparative analysis of expression and processing of the rat epididymal fluid and sperm-bound forms of proteins D and E. Biol. Reprod., 2002, 67(2), 525-533.
[http://dx.doi.org/10.1095/biolreprod67.2.525] [PMID: 12135891]
[9]
Kessler, R.J.; Fanestil, D.D. Interference by lipids in the determination of protein using bicinchoninic acid. Anal. Biochem., 1986, 159(1), 138-142.
[http://dx.doi.org/10.1016/0003-2697(86)90318-0] [PMID: 3812993]
[10]
Smith, P.K.; Krohn, R.I.; Hermanson, G.T.; Mallia, A.K.H. G.F.; Provenzano, M.D.; Fujimoto, E.K.; M, G.N.; Olson, B.J.; Klenk, D.C. 3,160,641 1964 Hartmann atlas purification of isosorbide. Anal. Biochem., 1985, 150, 76-85.
[http://dx.doi.org/10.1016/0003-2697(85)90442-7] [PMID: 3843705]
[11]
Wiechelman, K.J.; Braun, R.D.; Fitzpatrick, J.D. Investigation of the bicinchoninic acid protein assay: Identification of the groups responsible for color formation. Anal. Biochem., 1988, 175(1), 231-237.
[http://dx.doi.org/10.1016/0003-2697(88)90383-1] [PMID: 3245570]
[12]
Brown, R.E.; Jarvis, K.L.; Hyland, K.J. Protein measurement using bicinchoninic acid: Elimination of interfering substances. Anal. Biochem., 1989, 180(1), 136-139.
[http://dx.doi.org/10.1016/0003-2697(89)90101-2] [PMID: 2817336]
[13]
Keller, A.; Pedemonte, E.; Willmouth, F.M. Macro-lattice from segregated amorphous phases of a three block copolymer. Nature, 1970, 225, 538-539.
[http://dx.doi.org/10.1038/225538a0] [PMID: 16056598]
[14]
Fairbanks, G.; Steck, T.L.; Wallach, D.F.H. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry, 1971, 10(13), 2606-2617.
[http://dx.doi.org/10.1021/bi00789a030] [PMID: 4326772]
[15]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[16]
Metsalu, T.; Vilo, J. ClustVis: A web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic Acids Res., 2015, 43(W1)W566-70
[http://dx.doi.org/10.1093/nar/gkv468] [PMID: 25969447]
[17]
Snel, B.; Lehmann, G.; Bork, P.; Huynen, M.A. STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res., 2000, 28(18), 3442-3444.
[http://dx.doi.org/10.1093/nar/28.18.3442] [PMID: 10982861]
[18]
Szklarczyk, D.; Franceschini, A.; Kuhn, M.; Simonovic, M.; Roth, A.; Minguez, P.; Doerks, T.; Stark, M.; Muller, J.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res., 2011, 39(Database issue), D561-D568.
[http://dx.doi.org/10.1093/nar/gkq973] [PMID: 21045058]
[19]
Franceschini, A.; Szklarczyk, D.; Frankild, S.; Kuhn, M.; Simonovic, M.; Roth, A.; Lin, J.; Minguez, P.; Bork, P.; von Mering, C.; Jensen, L.J. STRING v9.1: Protein-protein interaction networks, Nucleic Acids Res., 2013, 41(Database issue), D808-D815.
[PMID: 23203871]
[20]
Szklarczyk, D.; Franceschini, A.; Wyder, S.; Forslund, K.; Heller, D.; Huerta-Cepas, J.; Simonovic, M.; Roth, A.; Santos, A.; Tsafou, K.P.; Kuhn, M.; Bork, P.; Jensen, L.J.; von Mering, C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res., 2015, 43(Database issue), D447-D452.
[http://dx.doi.org/10.1093/nar/gku1003] [PMID: 25352553]
[21]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937] [PMID: 27924014]
[22]
Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; Jensen, L.J.; Mering, C.V. STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res., 2019, 47(D1), D607-D613.
[http://dx.doi.org/10.1093/nar/gky1131] [PMID: 30476243]
[23]
STATISTICA Help | General Discriminant Analysis (GDA) Models. https://documentation.statsoft.com/STATISTICAHelp.aspx?path=Gxx/Indices/GeneralDiscriminantAnalysisModels_HIndex (accessed Oct 7, 2019).
[24]
Jiang, Y.; Sun, A.; Zhao, Y.; Ying, W.; Sun, H.; Yang, X.; Xing, B.; Sun, W. Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma. Nature, 2019, 567, 257-261.
[http://dx.doi.org/10.1038/s41586-019-0987-8]
[25]
Zhang, Q.; Chao, T.C.; Patil, V.S.; Qin, Y.; Tiwari, S.K.; Chiou, J.; Dobin, A.; Tsai, C.M.; Li, Z.; Dang, J.; Gupta, S.; Urdahl, K.; Nizet, V.; Gingeras, T.R.; Gaulton, K.J.; Rana, T.M. The long noncoding RNA ROCKI regulates inflammatory gene expression. EMBO J., 2019, 38(8), 1-18.
[http://dx.doi.org/10.15252/embj.2018100041] [PMID: 30918008]
[26]
Wheelwright, M.; Kim, E.W.; Inkeles, M.S.; De Leon, A.; Pellegrini, M.; Krutzik, S.R.; Liu, P.T. All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2. J. Immunol., 2014, 192(5), 2280-2290.
[http://dx.doi.org/10.4049/jimmunol.1301686] [PMID: 24501203]
[27]
Kim, E.W.; De Leon, A.; Jiang, Z.; Radu, R.A.; Martineau, A.R.; Chan, E.D.; Bai, X.; Su, W-L.; Montoya, D.J.; Modlin, R.L.; Liu, P.T.; Vitamin, A. vitamin a metabolism by dendritic cells triggers an antimicrobial response against Mycobacterium tuberculosis. MSphere, 2019, 4(3), 4.
[http://dx.doi.org/10.1128/mSphere.00327-19] [PMID: 31167948]
[28]
Anand, P.K.; Kaul, D.; Sharma, M. Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria. J. Microbiol. Immunol. Infect., 2008, 41(1), 17-25.
[PMID: 18327422]
[29]
Costet, P.; Lalanne, F.; Gerbod-Giannone, M.C.; Molina, J.R.; Fu, X.; Lund, E.G.; Gudas, L.J.; Tall, A.R. Retinoic acid receptor-mediated induction of ABCA1 in macrophages. Mol. Cell. Biol., 2003, 23(21), 7756-7766.
[http://dx.doi.org/10.1128/MCB.23.21.7756-7766.2003] [PMID: 14560020]
[30]
Crowle, A.J.; Ross, E.J. Inhibition by retinoic acid of multiplication of virulent tubercle bacilli in cultured human macrophages. Infect. Immun., 1989, 57(3), 840-844.
[PMID: 2492972]
[31]
Xu, L.L.; Fu, H.X.; Zhang, J.M.; Feng, F.E.; Wang, Q.M.; Zhu, X.L.; Xue, J.; Wang, C.C.; Chen, Q.; Liu, X.; Wang, Y.Z.; Qin, Y.Z.; Kong, Y.; Chang, Y.J.; Xu, L.P.; Liu, K.Y.; Huang, X.J.; Zhang, X.H. Impaired function of bone marrow mesenchymal stem cells from immune thrombocytopenia patients in inducing regulatory dendritic cell differentiation through the notch-1/Jagged-1 Signaling pathway. Stem Cells Dev., 2017, 26(22), 1648-1661.
[http://dx.doi.org/10.1089/scd.2017.0078] [PMID: 28946811]
[32]
Xiao, L.; Erb, U.; Zhao, K.; Hackert, T.; Zöller, M. Efficacy of vaccination with tumor-exosome loaded dendritic cells combined with cytotoxic drug treatment in pancreatic cancer. OncoImmunology, 2017, 6(6)e1319044
[http://dx.doi.org/10.1080/2162402X.2017.1319044] [PMID: 28680753]
[33]
Patties, I.; Kortmann, R.D.; Menzel, F.; Glasow, A. Enhanced inhibition of clonogenic survival of human medulloblastoma cells by multimodal treatment with ionizing irradiation, epigenetic modifiers, and differentiation-inducing drugs. J. Exp. Clin. Cancer Res., 2016, 35(1), 94.
[http://dx.doi.org/10.1186/s13046-016-0376-1] [PMID: 27317342]
[34]
Jiang, P.; Ray, A.; Rybak, L.P.; Brenner, M.J. Role of STAT1 and oxidative stress in gentamicin-induced hair cell death in organ of corti. Otol. Neurotol., 2016, 37(9), 1449-1456.
[http://dx.doi.org/10.1097/MAO.0000000000001192] [PMID: 27631653]
[35]
Bene, K.; Varga, Z.; Petrov, V.O.; Boyko, N.; Rajnavolgyi, E. Gut Microbiota species can provoke both inflammatory and tolerogenic immune responses in human dendritic cells mediated by retinoic acid receptor alpha ligation. Front. Immunol., 2017, 8, 427.
[http://dx.doi.org/10.3389/fimmu.2017.00427] [PMID: 28458670]
[36]
Jiang, T.T.; Wang, C.; Wei, L.L.; Yu, X.M.; Shi, L.Y.; Xu, D.D.; Chen, Z.L.; Ping, Z.P.; Li, J.C. Serum protein gamma-glutamyl hydrolase, Ig gamma-3 chain C region, and haptoglobin are associated with the syndromes of pulmonary tuberculosis in traditional Chinese medicine. BMC Complement. Altern. Med., 2015, 15, 243.
[http://dx.doi.org/10.1186/s12906-015-0686-4] [PMID: 26198726]
[37]
Meena, L.S. An overview to understand the role of PE_PGRS family proteins in Mycobacterium tuberculosis H37 Rv and their potential as new drug targets. Biotechnol. Appl. Biochem., 2015, 62(2), 145-153.
[http://dx.doi.org/10.1002/bab.1266] [PMID: 24975480]
[38]
Pankov, R. Fibronectin at a GlancePankov, R. Fibronectin at a glance. J. Cell Sci., 2002, 115, 3861-3863.
[http://dx.doi.org/10.1242/jcs.00059] [PMID: 12244123]
[39]
Al Shammari, B.; Shiomi, T.; Tezera, L.; Bielecka, M.K.; Workman, V.; Sathyamoorthy, T.; Mauri, F.; Jayasinghe, S.N.; Robertson, B.D.; D’Armiento, J.; Friedland, J.S.; Elkington, P.T. The extracellular matrix regulates granuloma necrosis in tuberculosis. J. Infect. Dis., 2015, 212(3), 463-473.
[http://dx.doi.org/10.1093/infdis/jiv076] [PMID: 25676469]
[40]
Nathan, C.; Shiloh, M.U. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA, 2000, 97(16), 8841-8848.
[http://dx.doi.org/10.1073/pnas.97.16.8841] [PMID: 10922044]
[41]
Shiloh, M.U.; Nathan, C.F. Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria. Curr. Opin. Microbiol., 2000, 3(1), 35-42.
[http://dx.doi.org/10.1016/S1369-5274(99)00048-X] [PMID: 10679417]
[42]
Alvarez, M.N.; Peluffo, G.; Piacenza, L.; Radi, R. Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: Consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J. Biol. Chem., 2011, 286(8), 6627-6640.
[http://dx.doi.org/10.1074/jbc.M110.167247] [PMID: 21098483]
[43]
Inagaki, T.; Kusunoki, S.; Tabu, K.; Okabe, H.; Yamada, I.; Taga, T.; Matsumoto, A.; Makino, S.; Takeda, S.; Kato, K. Up-regulation of lymphocyte antigen 6 complex expression in side-population cells derived from a human trophoblast cell line HTR-8/SVneo. Hum. Cell, 2016, 29(1), 10-21.
[http://dx.doi.org/10.1007/s13577-015-0121-7 ] [PMID: 26223706]
[44]
Pan, J.; Chen, Y.; Mo, C.; Wang, D.; Chen, J.; Mao, X.; Guo, S.; Zhuang, J.; Qiu, S. Association of DSC3 mRNA down-regulation in prostate cancer with promoter hypermethylation and poor prognosis. PLoS One, 2014, 9(3)e92815
[http://dx.doi.org/10.1371/journal.pone.0092815] [PMID: 24664224]
[45]
Jonca, N.; Leclerc, E.A.; Caubet, C.; Simon, M.; Guerrin, M.; Serre, G. Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses. Eur. J. Dermatol., 2011, 21(Suppl. 2), 35-42.
[http://dx.doi.org/10.1684/ejd.2011.1264] [PMID: 21628128]
[46]
Niehaus, J.Z.; Good, M.; Jackson, L.E.; Ozolek, J.A.; Silverman, G.A.; Luke, C.J. Human SERPINB12 Is an abundant intracellular serpin expressed in most surface and glandular epithelia. J. Histochem. Cytochem. 2015, 63(11), 854-865.
[http://dx.doi.org/10.1369/0022155415600498] [PMID: 26220980]
[47]
Campbell, G.; Swamynathan, S.; Tiwari, A.; Swamynathan, S.K. The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production. Biochem. Biophys. Res. Commun., 2019, 517(4), 729-734.
[http://dx.doi.org/10.1016/j.bbrc.2019.07.123] [PMID: 31387745]
[48]
Perez-Riverol, Y.; Csordas, A.; Bai, J.; Bernal-Llinares, M.; Hewapathirana, S.; Kundu, D.J.; Inuganti, A.; Griss, J.; Mayer, G.; Eisenacher, M.; Pérez, E.; Uszkoreit, J.; Pfeuffer, J.; Sachsenberg, T.; Yilmaz, S.; Tiwary, S.; Cox, J.; Audain, E.; Walzer, M.; Jarnuczak, A.F.; Ternent, T.; Brazma, A.; Vizcaíno, J.A. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res., 2019, 47(D1), D442-D450..
[http://dx.doi.org/10.1093/nar/gky1106] [PMID: 30395289]

Rights & Permissions Print Cite
Article Metrics
31
© 2024 Bentham Science Publishers | Privacy Policy