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

Abstract:

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Zhou T,Wang T,Garcia JG

doi

10.1038/srep06107

subject

Has Abstract

pub_date

2014-08-22 00:00:00

pages

6107

issn

2045-2322

pii

srep06107

journal_volume

4

pub_type

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