Tumor Biology

, Volume 36, Issue 10, pp 7375–7384 | Cite as

Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma

  • Hui Liu
  • Licun Wu
  • Kai Ji
  • Wei Wang


Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient’s tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease.


Malignant pleural mesothelioma Biomarkers Prognosis Biology 



This work was supported by the National Natural Science Foundation of China (NSFC) (81473485) and the Shandong Provincial Natural Science Foundation (2014ZRE27321).

Conflicts of interest



  1. 1.
    Ismail-Khan R, Robinson LA, Williams Jr CC, et al. Malignant pleural mesothelioma: a comprehensive review. Cancer Control. 2006;13(4):255–63.PubMedGoogle Scholar
  2. 2.
    Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet. 2005;366(9483):397–408.CrossRefPubMedGoogle Scholar
  3. 3.
    Le GV, Takahashi K, Park EK, et al. Asbestos use and asbestos-related diseases in Asia: past, present and future. Respirology. 2011;16(5):767–75.CrossRefPubMedGoogle Scholar
  4. 4.
    Zucali PA, Ceresoli GL, De Vincenzo F, et al. Advances in the biology of malignant pleural mesothelioma. Cancer Treat Rev. 2011;37(7):543–58.CrossRefPubMedGoogle Scholar
  5. 5.
    Hollevoet K, Reitsma JB, Creaney J, et al. Serum mesothelin for diagnosing malignant pleural mesothelioma: an individual patient data meta-analysis. J Clin Oncol. 2012;30(13):1541–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Wu X, Li D, Liu L, et al. Serum soluble mesothelin-related peptide (SMRP): a potential diagnostic and monitoring marker for epithelial ovarian cancer. Arch Gynecol Obstet. 2014;289(6):1309–14.CrossRefPubMedGoogle Scholar
  7. 7.
    Bostancı Ö, Kemik Ö, Kemik A, et al. Preoperative serum levels of mesothelin in patients with colon cancer. Dis Markers. 2014;2014:161954.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Baba K, Ishigami S, Arigami T, et al. Mesothelin expression correlates with prolonged patient survival in gastric cancer. J Surg Oncol. 2012;105(2):195–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Ho M, Bera TK, Willingham MC, et al. Mesothelin expression in human lung cancer. Clin Cancer Res. 2007;13(5):1571–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Tozbikian G, Brogi E, Kadota K, et al. Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival. PLoS One. 2014;9(12):e114900.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ali A, Brown V, Denley S, et al. Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel. BMC Clin Pathol. 2014;14(1):35.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rump A, Morikawa Y, Tanaka M, et al. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem. 2004;279(10):9190–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Maeda M, Hino O. Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers. Pathol Int. 2006;56(11):649–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Sapede C, Gauvrit A, Barbieux I, et al. Aberrant splicing and protease involvement in mesothelin release from epithelioid mesothelioma cells. Cancer Sci. 2008;99(3):590–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Hellstrom I, Raycraft J, Kanan S, et al. Mesothelin variant 1 is released from tumor cells as a diagnostic marker. Cancer Epidemiol Biomarkers Prev. 2006;15(5):1014–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Bera TK, Pastan I. Mesothelin is not required for normal mouse development or reproduction. Mol Cell Biol. 2000;20(8):2902–6.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tang Z, Qian M, Ho M. The role of mesothelin in tumor progression and targeted therapy. Anticancer Agents Med Chem. 2013;13(2):276–80.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Robinson BW, Creaney J, Lake R, et al. Mesothelin-family proteins and diagnosis of mesothelioma. Lancet. 2003;362(9396):1612–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Hassan R, Remaley AT, Sampson ML, et al. Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancer. Clin Cancer Res. 2006;12(2):447–53.CrossRefPubMedGoogle Scholar
  20. 20.
    Creaney J, Francis RJ, Dick IM, et al. Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden. Clin Cancer Res. 2011;17(5):1181–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Wheatley-Price P, Yang B, Patsios D, et al. Soluble mesothelin-related peptide and osteopontin as markers of response in malignant mesothelioma. J Clin Oncol. 2010;28(20):3316–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Cristaudo A, Foddis R, Vivaldi A, et al. Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer. Clin Cancer Res. 2007;13(17):5076–81.CrossRefPubMedGoogle Scholar
  23. 23.
    Grigoriu BD, Scherpereel A, Devos P, et al. Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment. Clin Cancer Res. 2007;13(10):2928–35.CrossRefPubMedGoogle Scholar
  24. 24.
    Schneider J, Hoffmann H, Dienemann H, et al. Diagnostic and prognostic value of soluble mesothelin-related proteins in patients with malignant pleural mesothelioma in comparison with benign asbestosis and lung cancer. J Thorac Oncol. 2008;3(11):1317–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Linch M, Gennatas S, Kazikin S, et al. A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice. BMC Cancer. 2014;14:674.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hollevoet K, Nackaerts K, Gosselin R, et al. Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma. J Thorac Oncol. 2011;6(11):1930–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Hollevoet K, Nackaerts K, Thas O, et al. The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor. Chest. 2012;141(2):477–84.CrossRefPubMedGoogle Scholar
  28. 28.
    Creaney J, Dick IM, Meniawy TM, et al. Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma. Thorax. 2014;69(10):895–902.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yamada S, Tabata C, Tabata R, et al. Clinical significance of pleural effusion mesothelin in malignant pleural mesothelioma. Clin Chem Lab Med. 2011;49(10):1721–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Creaney J, Yeoman D, Naumoff LK, et al. Soluble mesothelin in effusions: a useful tool for the diagnosis of malignant mesothelioma. Thorax. 2007;62(7):569–76.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Yamaguchi N, Hattori K, Oh-eda M, et al. A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5. J Biol Chem. 1994;269(2):805–8.PubMedGoogle Scholar
  32. 32.
    Shiomi K, Miyamoto H, Segawa T, et al. Novel ELISA system for detection of N-ERC/mesothelin in the sera of mesothelioma patients. Cancer Sci. 2006;97(9):928–32.CrossRefPubMedGoogle Scholar
  33. 33.
    Creaney J, Sneddon S, Dick IM, et al. Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum. Dis Markers. 2013;35(2):119–27.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hollevoet K, Nackaerts K, Thimpont J, et al. Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma. Am J Respir Crit Care Med. 2010;181(6):620–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Pass HI, Lott D, Lonardo F, et al. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med. 2005;353(15):1564–73.CrossRefPubMedGoogle Scholar
  36. 36.
    Pantazopoulos I, Boura P, Xanthos T, et al. Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma. Eur Respir J. 2013;41(3):706–15.CrossRefPubMedGoogle Scholar
  37. 37.
    El-Tanani MK. Role of osteopontin in cellular signaling and metastatic phenotype. Front Biosci. 2008;13:4276–84.CrossRefPubMedGoogle Scholar
  38. 38.
    Tajima K, Ohashi R, Sekido Y, et al. Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene. 2010;29(13):1941–51.CrossRefPubMedGoogle Scholar
  39. 39.
    Ohashi R, Tajima K, Takahashi F, et al. Osteopontin modulates malignant pleural mesothelioma cell functions in vitro. Anticancer Res. 2009;29(6):2205–14.PubMedGoogle Scholar
  40. 40.
    Rai AJ, Flores RM, Mathew A, et al. Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels. Clin Chem Lab Med. 2010;48(2):271–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Cappia S, Righi L, Mirabelli D, et al. Prognostic role of osteopontin expression in malignant pleural mesothelioma. Am J Clin Pathol. 2008;130(1):58–64.CrossRefPubMedGoogle Scholar
  42. 42.
    Zhang Y, Marmorstein LY. Focus on molecules: fibulin-3 (EFEMP1). Exp Eye Res. 2010;90(3):374–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Obaya AJ, Rua S, Moncada-Pazos A, et al. The dual role of fibulins in tumorigenesis. Cancer Lett. 2012;325(2):132–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Luo R, Zhang M, Liu L, et al. Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis. PLoS One. 2013;8(8):e70511.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Hwang CF, Chien CY, Huang SC, et al. Fibulin-3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity. J Pathol. 2010;222(4):367–79.CrossRefPubMedGoogle Scholar
  46. 46.
    Song EL, Hou YP, Yu SP, et al. EFEMP1 expression promotes angiogenesis and accelerates the growth of cervical cancer in vivo. Gynecol Oncol. 2011;121(1):174–80.CrossRefPubMedGoogle Scholar
  47. 47.
    Chen J, Wei D, Zhao Y, et al. Overexpression of EFEMP1 correlates with tumor progression and poor prognosis in human ovarian carcinoma. PLoS One. 2013;8(11):e78783.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Tong JD, Jiao NL, Wang YX, et al. Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis. Neoplasma. 2011;58(5):441–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Pass HI, Levin SM, Harbut MR, et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med. 2012;367(15):1417–27.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Hollevoet K, Sharon E. Fibulin-3 as a biomarker for pleural mesothelioma. N Engl J Med. 2013;368(2):189.CrossRefPubMedGoogle Scholar
  51. 51.
    Lamote K, Baas P, van Meerbeeck JP. Fibulin-3 as a biomarker for pleural mesothelioma. N Engl J Med. 2013;368(2):189–90.CrossRefPubMedGoogle Scholar
  52. 52.
    Pass HI, Goparaju C. Fibulin-3 as a biomarker for pleural mesothelioma. N Engl J Med. 2013;368(2):190.PubMedGoogle Scholar
  53. 53.
    Tanrikulu AC, Abakay A, Kaplan MA, et al. A clinical, radiographic and laboratory evaluation of prognostic factors in 363 patients with malignant pleural mesothelioma. Respiration. 2010;80(6):480–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Stathopoulos GT, Zhu Z, Everhart MB, et al. Nuclear factor-κB affects tumor progression in a mouse model of malignant pleural effusion. Am J Respir Cell Mol Biol. 2006;34(2):142–50.CrossRefPubMedGoogle Scholar
  55. 55.
    Jagirdar R, Solenov EI, Hatzoglou C, et al. Gene expression profile of aquaporin 1 and associated interactors in malignant pleural mesothelioma. Gene. 2013;517(1):99–105.CrossRefPubMedGoogle Scholar
  56. 56.
    Yoshida T, Hojo S, Sekine S, et al. Expression of aquaporin-1 is a poor prognostic factor for stage II and III colon cancer. Mol Clin Oncol. 2013;1(6):953–8.PubMedPubMedCentralGoogle Scholar
  57. 57.
    El Hindy N, Bankfalvi A, Herring A, et al. Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma. Anticancer Res. 2013;33(2):609–13.PubMedGoogle Scholar
  58. 58.
    Chen R, Shi Y, Amiduo R, et al. Expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in women of Uygur ethnicity from Xinjiang, China. PloS One. 2014;9(2):e98576.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Esteva-Font C, Jin BJ, Verkman AS. Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice. FASEB J. 2014;28(3):1446–53.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    López-Campos JL, Sánchez Silva R, Gómez Izquierdo L, et al. Overexpression of Aquaporin-1 in lung adenocarcinomas and pleural mesotheliomas. Histol Histopathol. 2011;26(4):451–9.PubMedGoogle Scholar
  61. 61.
    Kao SC, Armstrong N, Condon B, et al. Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma. Cancer. 2012;118(11):2952–61.CrossRefPubMedGoogle Scholar
  62. 62.
    Richard V, Kindt N, Decaestecker C, et al. Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer. Oncol Rep. 2014;32(2):523–9.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Ji SQ, Su XL, Cheng WL, et al. Down-regulation of CD74 inhibits growth and invasion in clear cell renal cell carcinoma through HIF-1a pathway. Urol Oncol. 2014;32(2):153–61.CrossRefPubMedGoogle Scholar
  64. 64.
    Maharshak N, Cohen S, Lantner F, et al. CD74 is a survival receptor on colon epithelial cells. World J Gastroenterol. 2010;16(26):3258–66.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Cheng RJ, Deng WG, Niu CB, et al. Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma. Intl J Gynecol Cancer. 2011;21(6):1004–12.CrossRefGoogle Scholar
  66. 66.
    Morris KT, Nofchissey RA, Pinchuk IV, et al. Chronic macrophage migration inhibitory factor exposure induces mesenchymal epithelial transition and promotes gastric and colon cancers. PLoS One. 2014;9(6):e98656.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Otterstrom C, Soltermann A, Opitz I, et al. CD74: a new prognostic factor for patients with malignant pleural mesothelioma. Br J Cancer. 2014;110(8):2040–6.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Du W, Wright BM, Li X, et al. Tumor-derived macrophage migration inhibitory factor promotes an autocrine loop that enhances renal cell carcinoma. Oncogene. 2013;32(11):1469–74.CrossRefPubMedGoogle Scholar
  69. 69.
    Brock SE, Rendon BE, Yaddanapudi K, et al. Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas. J Biol Chem. 2012;287(45):37917–25.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Zhang JF, Hua R, Liu DJ, et al. Effect of CD74 on the prognosis of patients with resectable pancreatic cancer. Hepatobil Pancreat Dis Int. 2014;13(1):81–6.CrossRefGoogle Scholar
  71. 71.
    Lue H, Kapurniotu A, Fingerle-Rowson G, et al. Rapid andtransient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal. 2006;18(5):688–703.CrossRefPubMedGoogle Scholar
  72. 72.
    Leng L, Metz CN, Fang Y, et al. MIF signal transduction initiated by binding to CD74. J Expl Med. 2003;197(11):1467–76.CrossRefGoogle Scholar
  73. 73.
    Shi X, Leng L, Wang T, et al. CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25(4):595–606.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Lee CY, Su MJ, Huang CY, et al. Macrophage migration inhibitory factor increases cell motility and up‐regulates αvβ3 integrin in human chondrosarcoma cells. J Cell Biochem. 2012;113(5):1590–8.PubMedGoogle Scholar
  75. 75.
    Heinrichs D, Knauel M, Offermanns C, et al. Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74. Proc Natl Acad Sci U S A. 2011;108(42):17444–9.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Iwata T, Taniguchi H, Kuwajima M, et al. The action of D-dopachrome tautomerase as an adipokine in adipocyte lipid metabolism. PLoS One. 2012;7(3):e33402.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Park JJ, Seo SM, Kim EJ, et al. Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin β1 signaling. Biochem Biophys Res Commun. 2012;426(4):461–7.CrossRefPubMedGoogle Scholar
  78. 78.
    Chang HW, Lee YS, Nam HY, et al. Knockdown of beta-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines. Cell Signal. 2013;25(4):839–47.CrossRefPubMedGoogle Scholar
  79. 79.
    Kaur M, Deep G, Jain AK, et al. Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells. Carcinogenesis. 2013;34(7):1585–92.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Miyoshi H, Deguchi A, Nakau M, et al. Hepatocellular carcinoma development induced by conditional beta-catenin activation in Lkb1þ+/− mice. Cancer Sci. 2009;100(11):2046–53.CrossRefPubMedGoogle Scholar
  81. 81.
    Yang H, Rivera Z, Jube S, et al. Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation. Proc Natl Acad Sci U S A. 2010;107(28):12611–6.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81(1):1–5.CrossRefPubMedGoogle Scholar
  83. 83.
    Carbone M, Yang H. Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. Clin Cancer Res. 2012;18(3):598–604.CrossRefPubMedGoogle Scholar
  84. 84.
    Wang Y, Faux SP, Hallden G, et al. Interleukin-1 beta and tumour necrosis factor-alpha promote the transformation of human immortalised mesothelial cells by erionite. Int J Oncol. 2004;25(1):173–8.PubMedGoogle Scholar
  85. 85.
    Jube S, Rivera ZS, Bianchi ME, et al. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012;72(13):3290–301.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Qi F, Okimoto G, Jube S, et al. Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling. Am J Pathol. 2013;183(5):1654–66.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Tabata C, Shibata E, Tabata R, et al. Serum HMGB1 as a prognostic marker for malignant pleural mesothelioma. BMC Cancer. 2013;13:205.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Tabata C, Kanemura S, Tabata R, et al. Serum HMGB1 as a diagnostic marker for malignant peritoneal mesothelioma. J Clin Gastroenterol. 2013;47(8):684–8.CrossRefPubMedGoogle Scholar
  89. 89.
    Aggarwal S, Devaraja K, Sharma SC, et al. Expression of vascular endothelial growth factor (VEGF) in patients with oral squamous cell carcinoma and its clinical significance. Clin Chim Acta. 2014;436:35–40.CrossRefPubMedGoogle Scholar
  90. 90.
    Hansen W, Hutzler M, Abel S, et al. Neuropilin 1 deficiency on CD4+ Foxp3+ regulatory T cells impairs mouse melanoma growth. J Exp Med. 2012;209(11):2001–16.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Strizzi L, Catalano A, Vianale G, et al. Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol. 2001;193(4):468–75.CrossRefPubMedGoogle Scholar
  92. 92.
    Li Q, Yano S, Ogino H, et al. The therapeutic efficacy of anti vascular endothelial growth factor antibody, bevacizumab, and pemetrexed against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice. Clin Cancer Res. 2007;13(19):5918–25.CrossRefPubMedGoogle Scholar
  93. 93.
    Fiorelli A, Vicidomini G, Di Domenico M, et al. Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications. Interact Cardiovasc Thorac Surg. 2011;12(3):420–4.CrossRefPubMedGoogle Scholar
  94. 94.
    Tabata C, Tabata R, Kadokawa Y, et al. Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. J Immunol. 2007;179(1):708–14.CrossRefPubMedGoogle Scholar
  95. 95.
    Kumar-Singh S, Weyler J, Martin MJ, et al. Angiogenic cytokines in mesothelioma: a study of VEGF, FGF-1 and -2, and TGF beta expression. J Pathol. 1999;189(1):72–8.CrossRefPubMedGoogle Scholar
  96. 96.
    Demirag F, Unsal E, Yilmaz A, et al. Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma. Chest. 2005;128(5):3382–7.CrossRefPubMedGoogle Scholar
  97. 97.
    Aoe K, Hiraki A, Tanaka T, et al. Expression of vascular endothelial growth factor in malignant mesothelioma. Anticancer Res. 2006;26(6C):4833–6.PubMedGoogle Scholar
  98. 98.
    Yasumitsu A, Tabata C, Tabata R, et al. Clinical significance of serum vascular endothelial growth factor in malignant pleural mesothelioma. J Thorac Oncol. 2010;5(4):479–83.CrossRefPubMedGoogle Scholar
  99. 99.
    Hirayama N, Tabata C, Tabata R, et al. Pleural effusion VEGF levels as a prognostic factor of malignant pleural mesothelioma. Respir Med. 2011;105(1):137–42.CrossRefPubMedGoogle Scholar
  100. 100.
    Stayner L, Welch LS, Lemen R. The worldwide pandemic of asbestos-related diseases. Annu Rev Public Health. 2013;34:205–16.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Respiratory MedicineThe Second Hospital of Shandong UniversityJinanChina
  2. 2.Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General HospitalUniversity Health NetworkTorontoCanada
  3. 3.Department of EndocrinologyShengli Oilfield Central HospitalDongyingChina

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