Lipopolysaccharide‑binding protein is efficient in biodosimetry during radiotherapy of lung cancer

Chalubinska‑Fendler,Justyna; Fendler,Wojciech; Spych,Michal; Wyka,Krystyna; Luniewska‑Bury,Jolanta; Fijuth,Jacek

doi:10.3892/br.2016.739

Lipopolysaccharide‑binding protein is efficient in biodosimetry during radiotherapy of lung cancer

Authors:
- Justyna Chalubinska‑Fendler
- Wojciech Fendler
- Michal Spych
- Krystyna Wyka
- Jolanta Luniewska‑Bury
- Jacek Fijuth
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Affiliations: Department of Radiotherapy, Medical University of Łódź, 93‑509 Łódź, Poland, Department of Biostatistics and Translational Medicine, Medical University of Łódź, 91‑738 Łódź, Poland, Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Łódź, 91‑738 Łódź, Poland, Department of Brachytherapy, Regional Oncological Centre, 93‑509 Łódź, Poland
Published online on: August 8, 2016 https://doi.org/10.3892/br.2016.739
Pages: 450-454

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Abstract

The aim of the present study was to determine if the serum levels of early markers of inflammation, such as interleukin‑6 (IL‑6), tumor necrosis factor‑α (TNF‑α), C‑reactive protein (CRP), and lipopolysaccharide‑binding protein (LBP) were correlated with the radiation dose received by the pulmonary and mediastinal structures of patients with non‑small cell lung cancer (NSCLC). This pilot study included 26 patients with NSCLC who received total radiation doses ranging from 54 to 74 Gy (2.0 Gy/fraction). Cytokines were measured at baseline by enzyme‑linked immunosorbant assay, and following administration of total doses of 20 and 40 Gy. A control group of 26 participants was sampled for comparisons with patient baseline cytokine levels. Only data from the 40‑Gy cytokine blood levels of patients with NSCLC were identified to be correlated with histograms of the parameters of each patient's radiotherapy protocol. The IL‑6, TNF‑α and CRP median baseline levels of the patients with NSCLC were significantly higher than those of the controls (all P≤0.01). No differences were observed between the LBP levels of the patients and controls [median, 36.34 (25‑75%; 31.35‑39.27) vs. 36.92 (30.20‑44.05) µg/ml, respectively; P=0.42]. No significant differences in the levels of the four cytokines between baseline, and at 20 and 40 Gy were observed [IL‑6 (P=0.19); TNF‑α (P=0.68); CRP (P=0.44) and LBP (P=0.29)]. LBP was significantly and positively correlated with the mean radiation dose to the lung (r=0.409; P=0.038), and showed a positive correlation with the percentage of lung volume exposed to at least 20 Gy of the planned radiation dose (r=0.3536; P=0.0764). CRP levels were positively correlated with the mean radiation dose to the esophagus (r=0.404; P=0.041); however, IL‑6, TNF‑α and CRP were not significantly associated with other lung dosimetry parameters. Thus, LBP levels were correlated with radiation exposure of pulmonary tissues, and LBP may be a marker that warrants further investigation on radiotoxicity in NSCLC patients.

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1	Garipagaoglu M, Munley MT, Hollis D, Poulson JM, Bentel GC, Sibley G, Anscher MS, Fan M, Jaszczak RJ, Coleman RE, et al: The effect of patient-specific factors on radiation-induced regional lung injury. Int J Radiat Oncol Biol Phys. 45:331–338. 1999. View Article : Google Scholar : PubMed/NCBI
2	Claude L, Pérol D, Ginestet C, Falchero L, Arpin D, Vincent M, Martel I, Hominal S, Cordier JF and Carrie C: A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: Clinical and dosimetric factors analysis. Radiother Oncol. 71:175–181. 2004. View Article : Google Scholar : PubMed/NCBI
3	Kong FM, Ao X, Wang L and Lawrence TS: The use of blood biomarkers to predict radiation lung toxicity: A potential strategy to individualize thoracic radiation therapy. Cancer Control. 15:140–150. 2008.PubMed/NCBI
4	Abratt RP and Morgan GW: Lung toxicity following chest irradiation in patients with lung cancer. Lung Cancer. 35:103–109. 2002. View Article : Google Scholar : PubMed/NCBI
5	Marks LB, Bentzen SM, Deasy JO, Kong FM, Bradley JD, Vogelius IS, El Naqa I, Hubbs JL, Lebesque JV, Timmerman RD, et al: Radiation dose-volume effects in the lung. Int J Radiat Oncol Biol Phys. 76:(Suppl). S70–S76. 2010. View Article : Google Scholar : PubMed/NCBI
6	Rubin P, Finkelstein J and Shapiro D: Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: Interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys. 24:93–101. 1992. View Article : Google Scholar : PubMed/NCBI
7	Morgan GW and Breit SN: Radiation and the lung: A reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys. 31:361–369. 1995. View Article : Google Scholar : PubMed/NCBI
8	Siva S, MacManus M, Kron T, Best N, Smith J, Lobachevsky P, Ball D and Martin O: A pattern of early radiation-induced inflammatory cytokine expression is associated with lung toxicity in patients with non-small cell lung cancer. PLoS One. 9:e1095602014. View Article : Google Scholar : PubMed/NCBI
9	Chaturvedi AK, Caporaso NE, Katki HA, Wong HL, Chatterjee N, Pine SR, Chanock SJ, Goedert JJ and Engels EA: C-reactive protein and risk of lung cancer. J Clin Oncol. 28:2719–2726. 2010. View Article : Google Scholar : PubMed/NCBI
10	Hartsell WF, Scott CB, Dundas GS, Mohiuddin M, Meredith RF, Rubin P and Weigensberg IJ: Can serum markers be used to predict acute and late toxicity in patients with lung cancer? Analysis of RTOG 91–03. Am J Clin Oncol. 30:368–376. 2007. View Article : Google Scholar : PubMed/NCBI
11	Dehing-Oberije C, Aerts H, Yu S, De Ruysscher D, Menheere P, Hilvo M, van der Weide H, Rao B and Lambin P: 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. 81:360–368. 2011. View Article : Google Scholar : PubMed/NCBI
12	Walker MJ, Zhou C, Backen A, Pernemalm M, Williamson AJ, Priest LJ, Koh P, Faivre-Finn C, Blackhall FH, Dive C, et al: Discovery and validation of predictive biomarkers of survival for non-small cell lung cancer patients undergoing radical radiotherapy: Two proteins with predictive value. E Bio Medicine. 2:841–850. 2015.
13	Chen Y, Williams J, Ding I, Hernady E, Liu W, Smudzin T, Finkelstein JN, Rubin P and Okunieff P: Radiation pneumonitis and early circulatory cytokine markers. Semin Radiat Oncol. 12(Suppl 1): 26–33. 2002. View Article : Google Scholar : PubMed/NCBI
14	Mazeron R, Etienne-Mastroianni B, Pérol D, Arpin D, Vincent M, Falchero L, Martel-Lafay I, Carrie C and Claude L: Predictive factors of late radiation fibrosis: A prospective study in non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 77:38–43. 2010. View Article : Google Scholar : PubMed/NCBI
15	Wrona A and Jassem J: The new TNM classification in lung cancer. Pneumonol Alergol Pol. 78:407–417. 2010.(In Polish). PubMed/NCBI
16	Soriano JB, Lamprecht B, Ramírez AS, Martinez-Camblor P, Kaiser B, Alfageme I, Almagro P, Casanova C, Esteban C, Soler-Cataluña JJ, et al: Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: A pooled analysis of individual patient data. Lancet Respir Med. 3:443–450. 2015. View Article : Google Scholar : PubMed/NCBI
17	Miedinger D, Neukomm E, Chhajed PN, Schnyder A, Naef M, Ackermann M and Leuppi JD: The use of the Asthma Control Test in general practice and its correlation with asthma control according to the GINA guidelines. Curr Med Res Opin. 27:2301–2308. 2011. View Article : Google Scholar : PubMed/NCBI
18	National Comprehensive Cancer Network (NCCN), . NCCN Guidelines®. NCCN; Fort Washington, PA, USA: 2015
19	No authors listed: Prescribing, recording, and reporting photon-beam intensity-modulated radiation therapy (IMRT): Contents. J ICRU. 10(NP)2010.
20	Faria SL, Aslani M, Tafazoli FS, Souhami L and Freeman CR: The challenge of scoring radiation-induced lung toxicity. Clin Oncol (R Coll Radiol). 21:371–375. 2009. View Article : Google Scholar
21	Wolk K, Witte E, Hoffmann U, Doecke WD, Endesfelder S, Asadullah K, Sterry W, Volk HD, Wittig BM and Sabat R: IL-22 induces lipopolysaccharide-binding protein in hepatocytes: A potential systemic role of IL-22 in Crohn's disease. J Immunol. 178:5973–5981. 2007. View Article : Google Scholar : PubMed/NCBI
22	Abdolhosseini M, Sotsky JB, Shelar AP, Joyce PB and Gorr SU: Human parotid secretory protein is a lipopolysaccharide-binding protein: Identification of an anti-inflammatory peptide domain. Mol Cell Biochem. 359:1–8. 2012. View Article : Google Scholar : PubMed/NCBI
23	Villar J, Pérez-Méndez L, Espinosa E, Flores C, Blanco J, Muriel A, Basaldúa S, Muros M, Blanch L, Artigas A, et al: GRECIA and GEN-SEP Groups: Serum lipopolysaccharide binding protein levels predict severity of lung injury and mortality in patients with severe sepsis. PLoS One. 4:e68182009. View Article : Google Scholar : PubMed/NCBI
24	Dentener MA, Vreugdenhil AC, Hoet PH, Vernooy JH, Nieman FH, Heumann D, Janssen YM, Buurman WA and Wouters EF: Production of the acute-phase protein lipopolysaccharide-binding protein by respiratory type II epithelial cells: Implications for local defense to bacterial endotoxins. Am J Respir Cell Mol Biol. 23:146–153. 2000. View Article : Google Scholar : PubMed/NCBI
25	Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, et al: Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 28:2181–2190. 2010. View Article : Google Scholar : PubMed/NCBI
26	De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag M, Dingemans AM, Bootsma G, Geraedts W, Simons J, et al: Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: A prospective, population-based study. Ann Oncol. 20:98–102. 2009. View Article : Google Scholar : PubMed/NCBI