Genetic network and gene set enrichment analysis to identify biomarkers related to cigarette smoking and lung cancer

Cancer Treatment Reviews

Volumn 39, Issue 1, 2013, Pages 77-88

  Fang, Xiaocong ^a   Netzer, Michael ^b   Baumgartner, Christian ^b   Bai, Chunxue ^a   Wang, Xiangdong ^a  

^a FUDAN UNIVERSITY   (China)

^b UNIVERSITY FOR HEALTH SCIENCES   (Austria)

Author keywords

Biomarkers; Genes; Lung cancer; Networks; Smoking; Treatment

Indexed keywords

CYTOCHROME P450; DNA; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN PHOSPHATASE 1F; RNA; SEMAPHORIN; SEMAPHORIN 5A; TRANSCRIPTION FACTOR; TRANSCRIPTION REGULATOR 1; TUMOR MARKER; UNCLASSIFIED DRUG;

CANCER STAGING; DNA REPLICATION; ENDOCYTOSIS; ENDOPLASMIC RETICULUM; FEMALE; GENE EXPRESSION; GENETIC ANALYSIS; HUMAN; LUNG CANCER; MAJOR CLINICAL STUDY; MALE; REVIEW; RNA TRANSPORT; SMOKING; SMOOTH MUSCLE CONTRACTION; VASCULAR SMOOTH MUSCLE;

DATABASES, GENETIC; FEMALE; GENE REGULATORY NETWORKS; HUMANS; LUNG NEOPLASMS; MALE; NEOPLASM STAGING; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; SMOKING; TUMOR MARKERS, BIOLOGICAL;

EID: 84869086541     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.06.001     Document Type: Review

References (102)

1. Molina J.R., Yang P., Cassivi S.D., Schild S.E., Adjei A.A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008, 83:584-594.
2. Beane J., Vick J., Schembri F., Anderlind C., Gower A., Campbell J., et al. Characterizing the impact of smoking andlung canceron the airway transcriptome using RNA-Seq. Cancer Prev Res (Phila) 2011, 4:803-817.
3. Begum S. Molecular changes in smoking-related lung cancer. Expert Rev Mol Diagn 2012, 12:93-106.
4. Baumgartner C., Osl M., Netzer M., Baumgartner D. Bioinformatic-driven search for metabolic biomarkers in disease. J Clin Bioinform 2011, 1:1-10.
5. Wang X. Role of clinical bioinformatics in the development of network-based Biomarkers. J Clin Bioinforma 2011, 1:28.
6. Netzer M., Weinberger K.M., Handler M., Seger M., Fang X., Kugler K.G., et al. A computational strategy for the identification and kinetic analysis of metabolic biomarkers: a pilot study for profiling human response to physical exercise. J Clin Bioinforma 2011, 1:34.
7. Sienel W., Dango S., Ehrhardt P., Eggeling S., Kirschbaum A., Passlick B. The future in diagnosis and staging of lung cancer. Molecular techniques. Respiration 2006, 73:575-580.
8. Goldenberg A., Mostafavi S., Quon G., Boutros P.C., Morris Q.D. Unsupervised detection of genes of influence in lung cancer using biological networks. Bioinformatics 2011, 27:3166-3172.
9. Beane J., Vick J., Schembri F., Anderlind C., Gower A., Campbell J., et al. Characterizing the impact of smoking andlung canceron the airway transcriptome using RNA-Seq. Cancer Prev Res (Phila) 2011, 4:803-817.
10. Wen J., Fu J., Zhang W., Guo M. Genetic and epigenetic changes in lung carcinoma and their clinical implications. Mod Pathol 2011, 24:932-943.
11. Kim B., Lee H.J., Choi H.Y., Shin Y., Nam S., Seo G., et al. Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data. Cancer Res 2007, 67:7431-7438.
12. Landi M.T., Dracheva T., Rotunno M., Figueroa J.D., Liu H., Dasgupta A., et al. Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival. PLoS One 2008, 3:e1651.
13. Netzer M, Fang X, Handler M, Baumgartner C. A coupled three-step network-based approach to identify genes associated with breast cancer. BIOTECHNO 2012, The Fourth International Conference on Bioinformatics, Biocomputational Systems and Biotechnologies 2012;1-5.
14. Quinlan J.R. Induction of decision trees. Mach Learn 1986, 1(1):81-106.
15. Hall M.A. Correlation-based feature selection for machine learning, Ph.D. dissertation, University of Waikato, 1999.
16. Subramanian A., Tamayo P., Mootha V.K., Mukherjee S., Ebert B.L., Gillette M.A., et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005, 102:15545-15550.
17. R Development Core Team, R. The R Project for Statistical Computing. Available: http://www.R-project.org.
18. Cline M.S., Smoot M., Cerami E., Kuchinsky A., Landys N., Workman C., et al. Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2007, 2(10):2366-2382.
19. Wang X., Chorley B.N., Pittman G.S., Kleeberger S.R., Brothers J., Liu G., et al. Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PLoS One 2010, 5:e11934.
20. Wang R., Wang G., Ricard M.J., Ferris B., Strulovici-Barel Y., Salit J., et al. Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals. Chest 2010, 138:1402-1410.
21. Ding H., Wang F., Ding X., Song X., Lu X., Zhang K., et al. Association study of semaphorin 5A with risk of Parkinson's disease in a Chinese Han population. Brain Res 2008, 1245:126-129.
22. Lu T.P., Tsai M.H., Lee J.M., Hsu C.P., Chen P.C., Lin C.W., et al. Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women. Cancer Epidemiol Biomarkers Prev 2010, 19:2590-2597.
23. Sadanandam A., Varney M.L., Kinarsky L., Ali H., Mosley R.L., Singh R.K. Identification of functional cell adhesion molecules with a potential role in metastasis by a combination of in vivo phage display and in silico analysis. OMICS 2007, 11:41-57.
24. Rose J.E., Behm F.M., Drgon T., Johnson C., Uhl G.R. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Mol Med 2010, 16:247-253.
25. Susila A., Chan H., Loh A.X., Phang H.Q., Wong E.T., Tergaonkar V., et al. The POPX2 phosphatase regulates cancer cell motility and invasiveness. Cell Cycle 2010, 9:179-187.
26. Chen J.J., London I.M. Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase. Trends Biochem Sci 1995, 20:105-108.
27. Koumenis C., Wouters B.G. "Translating" tumor hypoxia: unfolded protein response (UPR)-dependent and UPR-independent pathways. Mol Cancer Res 2006, 4:423-436.
28. Liu Y., László C., Liu Y., Liu W., Chen X., Evans S.C., et al. Regulation of G(1) arrest and apoptosis in hypoxia by PERK and GCN2-mediated eIF2alpha phosphorylation. Neoplasia 2010, 12:61-68.
29. Pataer A., Raso M.G., Correa A.M., Behrens C., Tsuta K., Solis L., et al. Prognostic significance of RNA-dependent protein kinase on non-small cell lung cancer patients. Clin Cancer Res 2010, 16:5522-5528.
30. Hengstermann A., Müller T. Endoplasmic reticulum stress induced by aqueous extracts of cigarette smoke in 3T3 cells activates the unfolded-protein-response-dependent PERK pathway of cell survival. Free Radic Biol Med 2008, 44:1097-1107.
31. Tagawa Y., Hiramatsu N., Kato H., Sakoh T., Nakajima S., Hayakawa K., et al. Toxicology: Induction of CCAAT/enhancer-binding protein-homologous protein by cigarette smoke through the superoxide anion-triggered PERK-eIF2α pathway. Toxicology 2011, 287:105-112.
32. Hayes G.M., Carrigan P.E., Beck A.M., Miller L.J. Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res 2006, 66:3819-3827.
33. Hayes G.M., Carrigan P.E., Miller L.J. Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas. Cancer Res 2007, 67:2072-2080.
34. Weber G.F. The cancer biomarker osteopontin: combination with other markers. Cancer Genomics Proteomics 2011, 8:263-288.
35. Das R., Mahabeleshwar G.H., Kundu G.C. Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. J Biol Chem 2004, 279:11051-11064.
36. Delimpoura V., Bakakos P., Tseliou E., Bessa V., Hillas G., Simoes D.C., et al. Increased levels of osteopontin in sputum supernatant in severe refractory asthma. Thorax 2010, 65:782-786.
37. Sottrup-Jensen L. Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation. J Biol Chem 1989, 264:11539-11542.
38. Marchandise F.X., Mathieu B., Francis C., Sibille Y. Local increase of antiprotease and neutrophil elastase-alpha 1-proteinase inhibitor complexes in lung cancer. Eur Respir J 1989, 2:623-629.
39. Lim W., Jeong W., Kim J.H., Lee J.Y., Kim J., Bazer F.W., et al. Differential expression of alpha 2 macroglobulinin response to dietylstilbestrol and in ovarian carcinomas in chickens. Reprod Biol Endocrinol 2011, 9:137.
40. Suriyaprom K., Harnroongroj T., Namjuntra P., Chantaranipapong Y., Tungtrongchitr R. Effects of tobacco smoking on alpha-2-macroglobulin and some biochemical parameters in Thai males. Southeast Asian J Trop Med Public Health 2007, 38:918-926.
41. Goyal M.M., Basak A. Human catalase: looking for complete identity. Protein Cell 2010, 1:888-897.
42. Wülfing P., Diallo R., Kersting C., Wülfing C., Poremba C., Rody A., et al. Expression of endothelin-1, endothelin-A, and endothelin-B receptor in human breast cancer and correlation with long-term follow-up. Clin Cancer Res 2003, 9:4125-4131.
43. Zhou L., Feng X., Shan W., Zhou W., Liu W., Wang L., et al. Epigenetic and genetic alterations of the EDNRB gene in nasopharyngeal carcinoma. Oncology 2007, 72:357-363.
44. Knight L.J., Burrage J., Bujac S.R., Haggerty C., Graham A., Gibson N.J., et al. Epigenetic silencing of the endothelin-B receptor gene in non-small cell lung cancer. Int J Oncol 2009, 34:465-471.
45. Chen S.C., Lin C.Y., Chen Y.H., Fang H.Y., Cheng C.Y., Chang C.W., et al. Aberrant promoter methylation of EDNRB in lung cancer in Taiwan. Oncol Rep 2006, 15:167-172.
46. Taillé C., Guénégou A., Almolki A., Piperaud M., Leynaert B., Vuillaumier S., et al. ETB receptor polymorphism is associated with airway obstruction. BMC Pulm Med 2007, 7:5.
47. Wikenheiser K.A., Vorbroker D.K., Rice W.R., Clark J.C., Bachurski C.J., Oie H.K., et al. Production of immortalized distal respiratory epithelial cell lines from surfactant protein C/simian virus 40 large tumor antigen transgenic mice. Proc Natl Acad Sci U S A 1993, 90:11029-11033.
48. Stenger P.C., Alonso C., Zasadzinski J.A., Waring A.J., Jung C.L., Pinkerton K.E. Environmental tobacco smoke effects on lung surfactant film organization. Biochim Biophys Acta 2009, 1788:358-370.
49. Dejana E., Tournier-Lasserve E., Weinstein B.M. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 2009, 16:209-221.
50. Li H., Shi X., Liu J., Hu C., Zhang X., Liu H., et al. The soluble fragment of VE-cadherin inhibits angiogenesis by reducing endothelial cell proliferation and tube capillary formation. Cancer Gene Ther 2010, 17:700-707.
51. Barbieri S.S., Ruggiero L., Tremoli E., Weksler B.B. Suppressing PTEN activity by tobacco smoke plus interleukin-1beta modulates dissociation of VE-cadherin/beta-catenin complexes in endothelium. Arterioscler Thromb Vasc Biol 2008, 28:732-738.
52. Zeller C., Hinzmann B., Seitz S., Prokoph H., Burkhard-Goettges E., Fischer J., et al. SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breastcancer. Oncogene 2003, 22:2972-2983.
53. Timofeeva M.N., Kropp S., Sauter W., Beckmann L., Rosenberger A., Illig T., et al. CYP450 polymorphisms as risk factors for early-onset lung cancer: gender-specific differences. Carcinogenesis 2009, 30:1161-1169.
54. Wenzlaff A.S., Cote M.L., Bock C.H., Land S.J., Santer S.K., Schwartz D.R., et al. CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study. Carcinogenesis 2005, 26:2207-2212.
55. Errani C., Zhang L., Sung Y.S., Hajdu M., Singer S., Maki R.G., et al. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer 2011, 50:644-653.
56. Balasenthil S., Chen N., Lott S.T., Chen J., Carter J., Grizzle W.E., et al. A migration signature and plasma biomarker panel for pancreatic adenocarcinoma. Cancer Prev Res (Phila) 2011, 4:137-149.
57. Suzuki T., Nakamoto T., Ogawa S., Seo S., Matsumura T., Tachibana K., et al. MICAL, a novel CasL interacting molecule, associates with vimentin. J Biol Chem 2002, 277:14933-14941.
58. Ashida S., Furihata M., Katagiri T., Tamura K., Anazawa Y., Yoshioka H., et al. Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression. Clin Cancer Res 2006, 12:2767-2773.
59. Habedanck R., Stierhof Y.D., Wilkinson C.J., Nigg E.A. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 2005, 7:1140-1146.
60. Kleylein-Sohn J., Westendorf J., Le Clech M., Habedanck R., Stierhof Y.D., Nigg E.A. Plk4-induced centriole biogenesis in human cells. Dev Cell 2007, 13:190-202.
61. Sun Y. P53 and its downstream proteins as molecular targets ofcancer. Mol Carcinog 2006, 45:409-415.
62. Guo Y., Fu P., Zhu H., Reed E., Remick S.C., Petros W., et al. Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. Oncol Rep 2012, 27:286-292.
63. Radak Z., Goto S., Nakamoto H., Udud K., Papai Z., Horvath I. Lung cancer in smoking patients inversely alters the activity of hOGG1 and hNTH1. Cancer Lett 2005, 219:191-195.
64. Cheng L., Lu W., Kulkarni B., Pejovic T., Yan X., Chiang J.H., et al. Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies. Gynecol Oncol 2011, 117:159-169.
65. Taylor M., Moore K., Murray J., Aves S.J., Price C. Mcm10 interacts with Rad4/Cut5(TopBP1) and its association with origins of DNA replication is dependent on Rad4/Cut5(TopBP1). DNA Repair 2011, 10:1154-1163.
66. Lim H.J., Jeon Y., Jeon C.H., Kim J.H., Lee H. Targeted disruption of Mcm10 causes defective embryonic cell proliferation and early embryo lethality. Biochim Biophys Acta 2011, 1813:1777-1783.
67. Kilmartin J.V. Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication. J Cell Biol 2003, 162:1211-1221.
68. Wu C.C., Tsai F.M., Shyu R.Y., Tsai Y.M., Wang C.H., Jiang S.Y. G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells. BMC Cancer 2011, 11:175.
69. Kim J.I., Chakraborty P., Wang Z., Daaka Y. G-protein coupled receptor kinase 5 regulates prostate tumor growth. J Urol 2012, 187:322-329.
70. Yue W., Dacic S., Sun Q., Landreneau R., Guo M., Zhou W., et al. Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clin Cancer Res 2007, 13:4336-4344.
71. Kaafarani I., Fernandez-Sauze S., Berenguer C., Chinot O., Delfino C., Dussert C., et al. Targeting adrenomedullin receptors with systemic delivery of neutralizing antibodies inhibits tumor angiogenesis and suppresses growth of human tumor xenografts in mice. FASEB J 2009, 23:3424-3435.
72. Yagi R., Tanaka M., Sasaki K., Kamata R., Nakanishi Y., Kanai Y., et al. ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion. Oncogene 2011, 30:1413-1421.
73. Ma L., Mondal A.K., Murea M., Sharma N.K., Tönjes A., Langberg K.A., et al. The effect of ACACB cis-variants on gene expression and metabolic traits. PLoS One 2011, 6:e23860.
74. Ateeq B., Tomlins S.A., Chinnaiyan A.M. AGTR1 as a therapeutic target in ER-positive and ERBB2-negative breast cancer cases. Cell Cycle 2009, 8:3794-3795.
75. Xi B., Zeng T., Liu L., Liang Y., Liu W., Hu Y., et al. Association between polymorphisms of the renin-angiotensin system genes and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 2011, 130:561-568.
76. Cavalieri D., Dolara P., Mini E., Luceri C., Castagnini C., Toti S., et al. Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer. Oncol Res 2007, 16:535-548.
77. Deng Y.B., Nagae G., Midorikawa Y., Yagi K., Tsutsumi S., Yamamoto S., et al. Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. Cancer Sci 2010, 101:1501-1510.
78. Ho C.C., Kuo S.H., Huang P.H., Huang H.Y., Yang C.H., Yang P.C. Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer 2008, 59:105-110.
79. Wikman H., Seppänen J.K., Sarhadi V.K., Kettunen E., Salmenkivi K., Kuosma E., et al. Caveolins as tumour markers in lung cancer detected by combined use of cDNA and tissue microarrays. J Pathol 2004, 203:584-593.
80. Matakidou A., El Galta R., Rudd M.F., Webb E.L., Bridle H., Eisen T., et al. Further observations on the relationship between the FGFR4 Gly388Arg polymorphism and lung cancer prognosis. Br J Cancer 2007, 96:1904-1907.
81. Frullanti E., Berking C., Harbeck N., Jézéquel P., Haugen A., Mawrin C., et al. Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor. Eur J Cancer Prev 2011, 20:340-347.
82. Borczuk A.C., Sole M., Lu P., Chen J., Wilgus M.L., Friedman R.A., et al. Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor. Cancer Res 2011, 71:6665-6675.
83. Huang Z, Cheng Y, Chiu PM, Cheung FM, Nicholls JM, Kwong DL, et al. Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties. Oncogene 2011 Dec 12. [Epub ahead of print]. doi:10.1038/onc.2011.529.
84. Xu Q.Y., Gao Y., Liu Y., Yang W.Z., Xu X.Y. Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro. Chin Med J (Engl) 2008, 121:1830-1837.
85. Lee H., Deng J., Kujawski M., Yang C., Liu Y., Herrmann A., et al. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med 2010, 16:1421-1428.
86. Li Y., Geng J., Wang Y., Lu Q., Du Y., Wang W., et al. The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients. J Cancer Res Clin Oncol 2012, 138:311-316.
87. Koch M., Hussein F., Woeste A., Gründker C., Frontzek K., Emons G., et al. CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo. Breast Cancer Res Treat 2011, 128:337-346.
88. Tabernero M.D., Espinosa A.B., Maillo A., Rebelo O., Vera J.F., Sayagues J.M., et al. Patient gender is associated with distinct patterns of chromosomal abnormalities and sex chromosome linked gene-expression profiles in meningiomas. Oncologist 2007, 12:1225-1236.
89. Rapaport F., Zinovyev A., Dutreix M., Barillot E., Vert J.P. Classification of microarray data using gene networks. BMC Bioinformatics 2007, 8:35.
90. Tian Z., Hwang T., Kuang R. A hypergraph-based learning algorithm for classifying gene expression and array CGH data with prior knowledge. Bioinformatics 2009, 25:2831-2838.
91. Wang Y.C., Chen B.S. A network-based biomarker approach for molecular investigation and diagnosis of lung cancer. BMC Med Genomics 2011, 4:2.
92. Bai J., Hu S. Transcriptome network analysis reveals potential candidate genes for squamous lung cancer. Int J Mol Med 2012, 29:95-101.
93. Zhao H., Adler K.B., Bai C., Tang F., Wang X.D. Epithelial proteomics in multiple organs and tissues: similarities and variations between cells, organs, and diseases. J Proteome Res 2006, 5:743-755.
94. Wang X.D., Adler K.B., Chaudry I.H., Ward P.A. Better understanding of organ dysfunction requires proteomic involvement. J Proteome Res 2006, 5:1060-1062.
95. Wu D., Rice C.M., Wang X. Cancer bioinformatics: a new approach to systems clinical medicine. BMC Bioinformatics 2012, 13:71.
96. López E., Wesselink J.J., López I., Mendieta J., Gómez-Puertas P., Muñoz S. Technical phosphoproteomic and bioinformatic tools useful in cancer research. J Clin Bioinform 2011, 1:26.
97. Chen H., Wang X.D. Significance of bioinformatics in research of chronic obstructive pulmonary disease. J Clin Bioinform 2011, 1:35.
98. Wu D.J., Zhu B.J., Wang X.D. Metabonomics-based omics study and atherosclerosis. J Clin Bioinform 2011, 1:30.
99. Yeh S.H., Yeh H.Y., Soo V.W. A network flow approach to predict drug targets from microarray data, disease genes and interactome network - case study on prostate cancer. J Clin Bioinform 2012, 2:1.
100. Chen H., Song Z., Qian M., Bai C., Wang X.D. Selection of disease-specific biomarkers by integrating inflammatory mediators with clinical informatics in AECOPD patients: a preliminary study. J Cell Mol Med 2012, 16:1286-1297.
101. Wang X.D. A new vision of clinical and translational medicine: definition, commentary, understanding. Clin Transl Med 2012, 1:5.
102. Wang X.D., Marincola F.M. A decade plus of translation: what do we understand?. Clin Transl Med 2012, 1:3.