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Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma.

Abstract
The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc-Ts that may significantly influence cancer biology, thus affecting cell differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high expression in several human cancers, closely associated with tumor progression and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting their clinical course and worse outcome, the identification of clinically significant accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical GalNAc-T3 expression and various clinicopathological characteristics and recurrence using 110 paraffin-embedded tumor samples obtained from patients with surgically resected ESOSCC (T1-2N0). Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3 expression was considered to be strongly positive when 20 % or more of the cancer cells showed positive cytoplasmic staining. Consequently, a strong expression of GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to poor differentiation, the presence of lymphatic and vascular invasion, and recurrence. Univariate and multivariate analyses further demonstrated that the patients with a strong GalNAc-T3+ status had markedly lower disease-free survival (DFS) rates, especially within the first 2 years postoperatively. Therefore, GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its immunohistochemical detection potentially predicts a shorter DFS and may be a useful parameter for providing clinical management against ESOSCC in the early postoperative phase.
AuthorsYoshikazu Harada, Hiroto Izumi, Hirotsugu Noguchi, Akihiro Kuma, Yuichiro Kawatsu, Tomoko Kimura, Shohei Kitada, Hidetaka Uramoto, Ke-Yong Wang, Yasuyuki Sasaguri, Hiroshi Hijioka, Akihiko Miyawaki, Ryoichi Oya, Toshiyuki Nakayama, Kimitoshi Kohno, Sohsuke Yamada
JournalTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 1 Pg. 1357-68 (Jan 2016) ISSN: 1423-0380 [Electronic] Netherlands
PMID26296622 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (metabolism)
  • Carcinoma, Squamous Cell (metabolism, mortality)
  • Cell Adhesion
  • Cell Differentiation
  • Cell Line, Tumor
  • Cytoplasm (metabolism)
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glycosylation
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Mouth Neoplasms (metabolism, mortality)
  • N-Acetylgalactosaminyltransferases (metabolism)
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins (metabolism)
  • Neoplasm Recurrence, Local
  • Prognosis
  • Young Adult

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