title: Combining factors on protein and gene level to predict radioresponse in head and neck cancer cell lines.
abstract: BACKGROUND
  Radiotherapy is the main therapy for head and neck squamous cell carcinoma (HNSCC); however, treatment resistance and local recurrence are significant problems, highlighting the need for predictive markers. In this study, we evaluated selected proteins, mutations, and single nucleotide polymorphisms (SNPs) involved in apoptosis, cell proliferation, and DNA repair alone or combined as predictive markers for radioresponse in 42 HNSCC cell lines.
  
  
  METHODS
  The expression of epidermal growth factor receptor, survivin, Bax, Bcl-2, Bcl-X(L) , cyclooxygenase-2 (COX-2), and heat shock protein 70 was analyzed by ELISA. Furthermore, mutations and SNPs in the p53 gene as well as SNPs in the MDM2, XRCC1, and XRCC3 genes were analyzed for their relation to radioresponse. To enable the evaluation of the predictive value of several factors combined, each cell line was allocated points based on the number of negative points (NNP) system, and the NNP sum was correlated with radioresponse.
  
  
  RESULTS
  Survivin was the only factor that alone was significantly correlated with the intrinsic radiosensitivity (IR; r = 0.36, P = 0.02). The combination of survivin, Bax, Bcl-2, Bcl-X(L) , COX-2, and the p53 Arg72Pro polymorphism was found to most strongly correlate with radioresponse (r = 0.553, P < 0.001).
  
  
  CONCLUSIONS
  These data indicate that the IR of 42 HNSCC cell lines can be predicted by a panel of factors on both the protein and gene levels. Moreover, among the investigated factors, survivin was the most promising biomarker of radioresponse.
authors.affiliation: Division of Otorhinolaryngology, Linköping University Hospital, Linköping, Sweden. lovisa.farnebo@lio.se
authors.forename: Lovisa
authors.initials: L
authors.lastname: Farnebo
authors.forename: Fredrik
authors.initials: F
authors.lastname: Jerhammar
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ceder
authors.forename: Roland C
authors.initials: RC
authors.lastname: Grafström
authors.forename: Linda
authors.initials: L
authors.lastname: Vainikka
authors.forename: Lena
authors.initials: L
authors.lastname: Thunell
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Johansson
authors.forename: Karin
authors.initials: K
authors.lastname: Roberg
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D001120:Arginine / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000145:classification; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000032:analysis; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D011392:Proline / Q000235:genetics; D011506:Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051020:bcl-X Protein / Q000032:analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D001120:Arginine; D011392:Proline; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C512478:EGFR protein, human; D066246:ErbB Receptors