A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer

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• 作者：C. Ostheimer (1)
  M. Bache (1)
  A. Güttler (1)
  M. Kotzsch (2)
  D. Vordermark (1)
  
• 关键词：Overall survival ; Hemoglobin ; Biological markers ; Vascular endothelial growth factor ; Prognostic factors ; Gesamtüberleben ; H?moglobin ; Biologische Marker ; Vaskul?rer endothelialer Wachstumsfaktor ; Prognosefaktoren
• 刊名：Strahlentherapie und Onkologie
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：190
• 期：3
• 页码：276-282
• 全文大小：497 KB
• 参考文献：1. H?ckel M, Vaupel P (2001) Biological consequences of tumor hypoxia. Semin Oncol 28:6-1 CrossRef
  2. Bayer C, Vaupel P (2012) Acute versus chronic hypoxia in tumors. Strahlenther Onkol 188:616-27 CrossRef
  3. Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225-39 CrossRef
  4. Zips D, B?ke S, Kroeber T et al (2011) Prognostic value of radiobiological hypoxia during fractionated irradiation for local tumor control. Strahlenther Onkol 187:306-10 CrossRef
  5. Vaupel P, Kelleher DK, H?ckel M (2001) Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 28:29-5 CrossRef
  6. Ostheimer C, Vordermark D (2013) Osteopontin—an indicator of tumor hypoxia and treatment resistance. In: Vordermark D (ed) Hypoxia: causes, types and management. Nova Publishers, New York
  7. Vordermark D, Brown JM (2003) Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? Strahlenther Onkol 179:801-11 CrossRef
  8. Le QT (2007) Identification and targeting hypoxia in head and neck cancer—a brief overview of current approaches. Int J Radiat Oncol Biol Phys 69:S56–S58 CrossRef
  9. Bache M, Kappler M, Said HM et al (2008) Detection and specific targeting of hypoxic regions within solid tumors: current preclinical and clinical strategies. Curr Med Chem 15:322-38 CrossRef
  10. Masahi U, Hideo S (2013) Visualization and treatment of the HIF-1-active microenvironments in tumors: drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments. In: Vordermark D (ed) Hypoxia: causes, types and management, 1st edn. Nova Publishers, New York, pp?221-35
  11. Schilling D, Bayer C, Emmerich K et al (2012) Basal HIF-1α expression levels are not predictive of radiosensitivity of human cancer cell lines. Strahlenther Onkol 188:353-58 CrossRef
  12. Le QT, Kong C, Lavori PW et al (2007) Expression and prognostic significance of a panel of tissue hypoxia markers in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 69:167-75 CrossRef
  13. Kim SJ, Rabbani ZN, Dewhirst MW et al (2005) Expression of HIF-1α, CA-IX, VEGF and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer 49:325-35 CrossRef
  14. Ilie M, Mazure NM, Hofman V et al (2010) High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer. Br J Cancer 25:1627-635 CrossRef
  15. Hoogsteen IJ, Marres HA, Bussink J et al (2007) Tumor microenvironment in head and neck squamous cell carcinoma: predictive value and clinical relevance of hypoxic markers. A review. Head Neck 29:591-04 CrossRef
  16. Zhu Y, Denhardt DT, Cao H et al (2005) Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer. Oncogene 24:6555-563
  17. Le QT, Chen E, Salim A et al (2006) An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res 12:1507-514 CrossRef
  18. Overgaard J, Eriksen JG, Nordsmark M et al (2005) Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial. Lancet Oncol 6:757-64 CrossRef
  19. Mack PC, Redman MW, Chansky K et al (2008) SWOG: Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol 26:4771-776 CrossRef
  20. Blasberg JD, Pass HI, Goparaju CM et al (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28:936-41 CrossRef
  21. Raja R, Kale S, Thorat D et al (2013) Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF-1α-mediated VEGF-dependent angiogenesis. Oncogene doi:10.1038/onc.2013.171
  22. Senger DR, Ledbetter SR, Claffey KP et al (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the av b 3 integrin osteopontin, and thrombin. Am J Pathol 149:293-05
  23. Solberg TD, Nearman J, Mullins J et al (2008) Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy. Int J Radiat Oncol Biol Phys 72:918-26 CrossRef
  24. Zhao X, Liu X, Guo W et al (2010) Expression of carbonic anhydrase IX in NSCLC and its relationship with VEGF and Ki67 expression. Chin J Cancer 13:881-66
  25. Beasley NJ, Wykoff CC, Watson PH et al (2001) Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density. Cancer Res 61:5262-267
  26. Le QT, Sutphin PD, Raychaudhuri S et al (2003) Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin Cancer Res 9:59-7
  27. Snitcovsky I, Leit?o GM, Pasini FS et al (2009) Plasma osteopontin levels in patients with head and neck cancer undergoing chemoradiotherapy. Arch Otolaryngol Head Neck Surg 135:807-11 CrossRef
  28. Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539-49 CrossRef
  29. Helbig L, Yaromina A, Sriramareddy SN et al (2012) Prognostic value of HIF-1α expression during fractionated irradiation. Strahlenther Onkol 188:1031-037 CrossRef
  30. Dellas K, Bache M, Pigorsch SU (2008) Prognostic impact of HIF-1alpha expression in patients with definitive radiotherapy for cervival cancer. Strahlenther Onkol 284:169-74 CrossRef
  31. Bache M, Reddemann R, Said HM et al (2006) Immunohistochemical detection of osteopontin in advanced head and neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1-alpha-related markers, and hemoglobin levels. Int J Radiat Oncol Biol Phys 66:1481-487 CrossRef
  32. Dunst J, Becker A, Lautenschl?ger C (2002) Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF). Strahlenther Onkol 178:436-41 CrossRef
  33. Dunst J, Stadler P, Becker A et al (2001) Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers. Strahlenther Onkol 177:469-73 CrossRef
  34. Vaupel P, Thews O, Hoeckel M (2001) Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 18:243-59 CrossRef
  35. Chang YS, Kim HJ, Chang J (2007) Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer. Lung Cancer 57:373-80 CrossRef
  36. Karadag F, Gulen ST, Karul AB et al (2011) Osteopontin as a marker of weight loss in lung cancer. Scand J Clin Lab Invest 71:690-94 CrossRef
  37. Bache M, Kappler M, Wichman H et al (2010) Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients. BMC Cancer 10:132-40 CrossRef
  38. Soliman M, Yaromina A, Appold S et al (2013) GTV differentially impacts locoregional control of non small-cell lung cancer (NSCLC) after different fractionation schedules: Subgroup analysis of the prospective randomized CHARTWELL trial. Radiother Oncol 106:299-04 CrossRef
  39. Ball DL, Fisher RJ, Burmeister BH et al (2013) The complex relationship between lung tumor volume and survival in patients with non small-cell lung cancer treated by definite radiotherapy: a prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305-11 CrossRef
  40. Bremnes RM, Camps C, Sirera R (2006) Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer 51:143-58 CrossRef
  41. Takenaka M, Hanagiri T, Shinohara S et al (2012) Serum level of osteopontin as a prognostic factor in patients who underwent surgical resection for non-small cell lung cancer. Clin Lung Cancer 31:S1525–S7304
  42. Potter CP, Harris AL (2003) Diagnostic, prognostic and therapeutic of carbonic anhydrases in cancer. Br J Cancer 89:2- CrossRef
  43. Mayer A, H?ckel M, Vaupel P (2008) Endogenous hypoxia markers: case not proven! Adv Exp Med Biol 614:127-36 CrossRef
  44. Weber GF (2011) The cancer biomarker osteopontin: combination with other markers. Cancer Genomics Proteomics 8:263-88
  45. De Schutter H, Landuyt W, Verbeken E et al (2005) The prognostic value of the hypoxia markers CA IX and GLUT I and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy. BMC Cancer 5:42-3 CrossRef
  46. Byers LA, Holsinger FC, Kies MS et al (2010) Serum signature of hypoxia-regulated factors is associated with progression after induction therapy in head and neck squamous cell cancer. Mol Cancer Ther 9:1755-763 CrossRef
  47. Yaromina A, Quennet V, Zips D et al (2009) Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human suqmous cell carcinoma (hSCC) xenografts. Int J Radiat Biol 85:971-80 CrossRef
  48. Zips D, Z?phel K, Abolmaali N et al (2012) Exploratory prospective trial of hypoxia-specific PET-imaging during radiochemotherapy in patients with locally advanced head-and-neack cancer. Radiother Oncol 105:21-8 CrossRef
  49. M?nnich D, Troost EG, Kaanders JH et al (2013) Correlation between tumor oxygenation and (18)F-fluoromisonidazole PET data simulated based on microvessel images. Acta Oncol 52:1308-313 CrossRef
  50. Erpolat, Gocun PO, Akmansu M et al (2013) Hypoxia-related molecules HIF-1α, CA9, and osteopontin. Predictors of survival in patients with high-grade glioma. Strahlenther Onkol 189:147-54 CrossRef
  51. Dehing-Oberije C, Aerts H, Yu S et al (2011) Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys 81:360-68 CrossRef
  52. Staab A, Fleischer M, Loeffler J et al (2011) Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro. Strahlenther Onkol 187:252-59 CrossRef
  53. Vordermark D (2010) Hypoxia-specific targets in cancer therapy: role of splice variants. BMC Med 12:1741-015
  
• 作者单位：C. Ostheimer (1)
  M. Bache (1)
  A. Güttler (1)
  M. Kotzsch (2)
  D. Vordermark (1)
  
  1. Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Dryanderstr. 4, 06110, Halle (Saale), Germany
  2. Department of Pathology, Technical University Dresden, Dresden, Germany
  
• ISSN：1439-099X

文摘

Background Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Material and methods Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55?NSCLC (M0) patients receiving 66?Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. Results All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p--.03), VEGF (p--.02) and CA IX (p--.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p--.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p--.03) in a multivariate Cox regression model including N stage, T stage and GTV. Conclusion This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated.