Plasma N -acetyl-glucosaminidase in advanced gastro-intestinal adenocarcinoma correlates with age, stage and outcome

Abstract

Background: N-acetyl-glucosaminidase (NAG) is a potential marker of genotoxicity. We retrospectively analyzed plasma NAG and clinico-pathologic features in advanced gastrointestinal adenocarcinoma patients. Methods: Plasma from 118 patients and 51 healthy volunteers was analyzed for associations between NAG levels and age, disease presence, stage, treatment responses and survival. Results: Pretreatment NAG correlated with age but was independently increased in metastatic versus locally advanced disease, particularly in gastric/esophageal patients. NAG was also associated with reduced overall survival. In subgroup analysis, increased NAG activity between day 1 and 2 of chemotherapy cycle 1 correlated with treatment response. Conclusion: We demonstrated that NAG correlates with gastrointestinal cancer outcomes. Further studies are required to determine if plasma markers of genotoxicity can be useful for disease monitoring. BackgroundBiological age is a risk factor in many cancers and the molecular factors underpinning cellular aging including telomere dysfunction and DNA damage responses have been shown to be common features at early stages of carcinogenesis [1]. These molecular events have been investigated in tumor samples by approaches including fluorescence hybridization and immunohistochemistry [2][3][4] and are intrinsically involved in cell aging and cellular senescence, correlating with tumor initiation of gastrointestinal tumors, such as adenocarcinoma of the stomach and colon [5]. There is considerable current interest in clinical application of markers of cellular senescence in cancer [6,7]. However, the 'senectome' is poorly defined and therefore there is a need to define the most appropriate markers for use in different settings. Furthermore, in clinical practice, there is a need for markers that are easy to measure in patient material and that are accessible to repeat sampling, ideally in blood for treatment monitoring.Recently, we described the identification of secreted proteins including the Chitinase enzyme N-acetyl-glucosaminidase (NAG) that are elevated in aging human fibroblasts preceding the onset of senescence and in response to DNA damage. NAG can be detected in human blood and increases with

A ‘synthetic-sickness’ screen for senescence re-engagement targets in mutant cancer backgrounds

“…However, to realise the full potential of candidate targets and markers identified in screening, appropriate routes to translation need to be established. We have previously investigated plasma markers of human ageing and DNA damage in gastrointestinal adenocarcinoma patients [ 51 ]. Furthermore, we have recently initiated two large, prospective, longitudinal studies to evaluate multiple candidate senescence biomarkers including ECT2 (UK Clinical Research Network trials 12434 and 12435).…”