Ku70 predicts response and primary tumor recurrence after therapy in locally advanced head and neck cancer.
5-Fluorouracil and cisplatin-based induction chemotherapy (IC) is commonly used to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The role of nonhomologous end joining (NHEJ) genes (Ku70, Ku80 and DNA-PKcs) in double-strand break (DSB) repair, genomic instability and apoptosis suggest a possible impact on tumor response to radiotherapy, 5-fluorouracil or cisplatin, as these agents are direct or indirect inductors of DSBs. We evaluated the relationship between Ku80, Ku70 or DNA PKcs mRNA expression in pretreatment tumor biopsies, and tumor response to IC or local recurrence, in 50 patients with HNSCC. Additionally, in an independent cohort of 75 patients with HNSCC, we evaluated the relationship between tumor Ku70 protein expression and the same clinical outcomes or patient survival. Tumors in the responder group had significantly higher mRNA levels for Ku70, Ku80 and DNA-PKcs than those in the nonresponder group. Ku70 mRNA was the marker most significantly associated with response to IC. Moreover, high tumor Ku70 mRNA expression was associated with significantly longer local recurrence-free survival (LRFS). Ku70 protein expression was also significantly related to response, and patients with higher percentage of tumor cells expressing Ku70 had longer LRFS. In addition, the percentage of Ku70 positive cells, tumor localization and node involvement were significantly associated with overall survival of patient. Therefore, Ku70 expression is a candidate predictive marker that could distinguish patients who are likely to benefit from chemoradiotherapy or radiotherapy after the induction chemotherapy treatment, suggesting a contribution of the NHEJ system in HNSCC clinical outcome.
Pavón
Miguel Angel
MA
Grup d'Oncogènesi i Antitumorals, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER) and Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Parreño
Matilde
M
León
Xavier
X
Sancho
Francesc J
FJ
Céspedes
Maria Virtudes
MV
Casanova
Isolda
I
Lopez-Pousa
Antonio
A
Mangues
Maria Antonia
MA
Quer
Miquel
M
Barnadas
Agustí
A
Mangues
Ramón
R
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D034961:Antigens, Nuclear / Q000032:analysis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen