title: Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and its correlation with tumor stage and with survivin/survivin DEx3 expression.
abstract: Nicotinamide phosphorybosiltransferase (NAMPT) plays an important role in the regulation of cellular growth, angiogenesis, and apoptosis in mammalian cells. NAMPT overexpression has been recently found in colorectal, breast, prostatic, gastric, esophageal, pancreatic cancers, and specific NAMPT inhibitors might be adjuvant therapeutic modalities. In this study, we analyzed NAMPT expression in 40 malignant and in 67 benign thyroid tissue samples using qPCR. We also investigated relationships between NAMPT expression and survivin/survivin splicing variants DEx3 and 2B expressions. NAMPT expression was significantly higher in thyroid cancers (P < 0.0001), and it was positively correlated with tumor stage (P = 0.0012; r = 0.493). NAMPT expression was significantly higher in tumors staged pT3 or pT4 (16 cases) than in tumors staged pT1 or pT2 (24 cases) (P = 0.0106). Metastases to the lymph nodes were found in 12 out of 40 cases, and NAMPT expression was higher in the metastatic group (P = 0.0258). Multifocality was not associated with higher NAMPT expression (P = 0.3451). NAMPT expression in thyroid cancers significantly correlated with survivin and with survivin splice variant DEx3 expressions (P < 0.0001; r = 0.624 and P = 0.0239; r = 0.357, respectively). There was no correlation between NAMPT and survivin 2B expressions (P = 0.3508). This is the first study demonstrating NAMPT overexpression in thyroid malignancies using quantitative RT-PCR. Moreover, it shows that NAMPT is upregulated in patients with more advanced tumor stage and metastatic disease which may prove to be clinically relevant. Further studies are needed to explain the role of NAMPT in thyroid cancer biology and the possible use of NAMPT inhibitors in thyroid cancer.
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewski St. 49, Poznań, Poland. nyha@tlen.pl.
authors.forename: Nadia
authors.initials: N
authors.lastname: Sawicka-Gutaj
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewski St. 49, Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Waligórska-Stachura
authors.affiliation: Department of Cell Biology, Poznan University of Medical Sciences, Rokietnicka St. 5d, Poznań, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Andrusiewicz
authors.affiliation: Department of General, Gastroenterological and Endocrine Surgery, Poznan University of Medical Sciences, Przybyszewski St. 49, Poznań, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Biczysko
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewski St. 49, Poznań, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sowiński
authors.affiliation: Department of General Surgery and Multiple Trauma, with Division of Gastroenterological and Endocrine Surgery, Provincial Hospital, Juraszów St. 7/19, Poznań, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Skrobisz
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewski St. 49, Poznań, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ruchała
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics*; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000077022:Survivin; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D016207:Cytokines; D051034:Inhibitor of Apoptosis Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D000077022:Survivin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human
keywords: Nicotinamide phosphoribosyltransferase; Nodular goiter; Reverse transcriptase polymerase chain reaction; Thyroid cancer; Thyroid gland; Visfatin