Expression of nicotinamide phosphoribosyltransferase-influenced genes predicts recurrence-free survival in lung and breast cancers.

TitleExpression of nicotinamide phosphoribosyltransferase-influenced genes predicts recurrence-free survival in lung and breast cancers.
Publication TypeJournal Article
Year of Publication2014
AuthorsZhou T, Wang T, Garcia JGN
JournalSci Rep
Volume4
Pagination6107
Date Published2014 Aug 22
ISSN Number2045-2322
KeywordsBreast Neoplasms, Female, Gene Expression Regulation, Neoplastic, Genome-Wide Association Study, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Male, Nicotinamide Phosphoribosyltransferase, Prognosis
Abstract

<p>Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide biosynthesis. NAMPT protein is a secreted plasma biomarker in inflammation and in cancer. The NAMPT enzymatic inhibitor, FK866, acts as an inducer of apoptosis and is a cancer therapeutic candidate, however, little is known regarding the influence of NAMPT on cancer biological mechanisms or on the prognosis of human cancers. We interrogated known microarray data sets to define NAMPT knockdown-influenced gene expression to demonstrate that reduced NAMPT expression strongly dysregulates cancer biology signaling pathways. Comparisons of gene expression datasets of four cancer types generated a N39 molecular signature exhibiting consistent dysregulated expression in multiple cancer tissues. The N39 signature provides a significant and independent prognostic tool of human recurrence-free survival in lung and breast cancers. Despite the absence of clear elucidation of molecular mechanisms, this study validates NAMPT as a novel "oncogene" with a central role in carcinogenesis. Furthermore, the N39 signature provides a potentially useful tool for prediction of recurrence-free survival in lung and breast cancer and validates NAMPT as a novel and effective therapeutic target in cancer.</p>

DOI10.1038/srep06107
Alternate JournalSci Rep
PubMed ID25146220
PubMed Central IDPMC4141256
Grant ListR01 HL094394 / HL / NHLBI NIH HHS / United States
R01HL094394 / HL / NHLBI NIH HHS / United States