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.

Survivin DEx3 as a biomarker of thyroid cancers: A study at the mRNA and protein level

“…To the best of our knowledge, this is the first study evaluating survivin DEx3 IHC expression in thyroid lesions. These findings are in agreement with our previous studies showing overexpression of survivin DEx3 mRNA in thyroid cancer (19,20). Using RT-qPCR, the present study also observed a positive association between the overexpression of survivin DEx3 mRNA and tumor aggressiveness.…”

“…By contrast, anti-apoptotic survivin DEx3 is suggested to be associated with tumor aggressiveness, advanced stage and poor prognosis in numerous types of cancer (5). We have previously reported survivin and its DEx3 mRNA variant overexpression in thyroid cancer (19,20).…”

“…no., 05 046 157 001; Roche Applied Science) served as reference reaction. qPCR was performed as previously described in a total reaction volume of 20 µl in a LightCycler ® 2.0 carousel based system (Roche Applied Science) (20). All reactions were made in triplicates with the hot start 1X LightCycler ® TaqMan ® Master mix (Roche Applied Science).…”

“…By contrast, anti-apoptotic survivin DEx3 is suggested to be associated with tumor aggressiveness, advanced stage and poor prognosis in numerous types of cancer (5). We have previously reported survivin and its DEx3 mRNA variant overexpression in thyroid cancer (19,20).Another nuclear protein, proliferating cell nuclear antigen (PCNA), is also involved in replication, so its level correlates with cellular proliferation (21).The aims of the present study were to confirm the findings on the overexpression of survivin and its DEx3 variant in thyroid cancer at the protein level using immunohistochemical (IHC) staining, and to evaluate the role of survivin and its splice variants DEx3 and 2B as potential biomarkers of thyroid malignancy. The present study additionally estimated the PCNA protein expression reflecting proliferative activity of tumors to better understand survivin and associated splice variant expression.…”

Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration

“…In cancer cells, NAMPT plays a crucial role in several physiological processes including energy generation, reductive biosynthesis, mitochondrial function, and the response to oxidative stress (1,(12)(13)(14). It is also overexpressed in several types of tumors (8,(15)(16)(17)(18)(19) and its expression appears to be associated with tumor progression (15,20). The inhibition of NAMPT leads to the attenuation of tumor growth and induction of apoptosis (11; 21-24).…”