Notch3 and Hey-1 as Prognostic Biomarkers in Pancreatic Adenocarcinoma

• DOI: 10.1371/journal.pone.0051119
• Publication Date: 2012-12-05T18:06:22Z
• Authors: Christopher D. Mann; Christopher Basti...; Christopher P. Neal; Muhammad M. Masood; Donald J. L. Jones; Friederike Teichert; Rajinder Singh; Elena Karpova; David P. Berry; Margaret M. Manson
• Keywords: Adult; Male; 0301 basic medicine; Notch; Science; 610; Cell Cycle Proteins; Adenocarcinoma; 03 medical and health sciences; Antigens, Neoplasm; Receptors; 80 and over; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Humans; Antigens; Pancreas; Proportional Hazards Models; Aged; Neoplasm Staging; Aged, 80 and over; Tumor; Q; R; Middle Aged; Prognosis; Survival Analysis; Immunohistochemistry; 3. Good health; Pancreatic Neoplasms; Treatment Outcome; Lymphatic Metastasis; Multivariate Analysis; Neoplasm; Medicine; Female; Peptides; Biomarkers; Signal Transduction; Research Article

In order to achieve a better outcome for pancreatic cancer patients, reliable biomarkers are required which allow improved diagnosis. These may emanate from more detailed molecular understanding of the aggressive nature this disease. Having previously reported that Notch3 activation appeared be associated with disease, we have now examined components pathway (Notch1, Notch3, Notch4, HES-1, HEY-1) in detail resectable (n = 42) and non-resectable 50) tumours compared uninvolved pancreas. All three Notch family members were significantly elevated tumour tissue, pancreas, expression maintained within matched lymph node metastases. Furthermore, higher nuclear Notch1, -3 -4, HEY-1 (all p≤0.001) was noted locally advanced metastatic cancers. survival analyses, reduced overall disease-free following resection curative intent, maintaining independent prognostic significance both outcomes on multivariate analysis. data further support central role signalling suggest its target gene, HEY-1, merit validation biomarker panels diagnosis, prognosis treatment efficacy. A peptide fragment detected plasma patients inoperable cancer, but due wide inter-individual variation, mean levels not different age-matched controls.