title: Deletion at Dickkopf (dkk)-3 locus (11p15.2) is related with lower lymph node metastasis and better prognosis in head and neck squamous cell carcinomas.
abstract: Head and neck squamous cell carcinoma (HNSCC) is a frequently occurring cancer, and despite improvement of its treatment methods, including chemotherapy, radiotherapy, and surgery, the improvement of survival remains poor. Recent advances in molecular biology of human cancer indicated various molecular abnormalities in HNSCC, including activation of oncogenes and inactivation of tumor suppressor genes (TSGs). Dickkopf (Dkk)-3 gene is known as a negative regulator of Wnt signaling and is suggested to function as TSG in several kinds of malignancies. We hypothesized that Dkk-3 might play an important role in HNSCC, too. Thus, in the current study, we analyzed allelic alteration of Dkk-3 locus (chromosome 11p15.2) by means of loss of heterozygosity (LOH) analysis. The study population consisted of 50 patients with HNSCC (mean age of 65 years old). Furthermore, we also examined the correlation between LOH findings of Dkk-3 locus with clinicopathological parameters to investigate its use as a biomarker in HNSCC. A remarkable LOH ratio (57%) was detected in the cases studied, implying that Dkk-3 is likely to be involved in HNSCC carcinogenesis. However, interestingly and in contrast to the expectations, we found that the group with LOH of Dkk-3 locus had less lymph node metastasis, and showed a favorable overall survival compared to the patients with retention of Dkk-3 area in survival analysis. These results indicate that Dkk-3 can play a role in HNSCC carcinogenesis with unknown mechanism. Moreover, allelic loss at Dkk-3 locus may also be used as a novel prognostic biomarker in HNSCC.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Katase
authors.forename: Mehmet
authors.initials: M
authors.lastname: Gunduz
authors.forename: Levent
authors.initials: L
authors.lastname: Beder
authors.forename: Esra
authors.initials: E
authors.lastname: Gunduz
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lefeuvre
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Hatipoglu
authors.forename: Silvia Susana
authors.initials: SS
authors.lastname: Borkosky
authors.forename: Ryo
authors.initials: R
authors.lastname: Tamamura
authors.forename: Susumu
authors.initials: S
authors.lastname: Tominaga
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000556:secondary*; D018925:Chemokines; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D017384:Sequence Deletion; D012737:Sex Factors; D012907:Smoking
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins