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J Surg Res. 2015 Aug;197(2):219-24. doi: 10.1016/j.jss.2014.11.002. Epub 2015 Apr 20.

The novel tumor angiogenic factor, adrenomedullin-2, predicts survival in pancreatic adenocarcinoma.

Author information

1
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut; Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut.
2
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
3
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut. Electronic address: Charles.cha@yale.edu.

Abstract

BACKGROUND:

Tumor angiogenesis has been demonstrated to have an important role in the development, progression, and metastasis of pancreas cancer. Adrenomedullin-2 (ADM2) is a calcitonin gene-related peptide that has recently been shown to be a novel tumor angiogenesis factor, acting via mitogen-activated protein kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/Akt, and vascular endothelial growth factor/vascular endothelial growth factor-2 signaling pathways. Through the use of tissue microarray (TMA) technology, we hypothesize that ADM2 is an important tumor angiogenesis factor in pancreatic cancer.

METHODS:

Multiple TMAs were created using tissue from pancreatic cancer patients resected between January 1996 and December 2006. Core tissue samples of formalin-fixed, paraffin-embedded blocks of pancreatic cancer tissue were collected through an institutional review board-approved protocol and linked to available clinicopathologic data. Two TMAs consisting of 112 and 60 patients with pancreatic adenocarcinoma were studied for ADM2 protein expression using a quantitative, automated immunofluorescent microscopy system, a technology that removes potential observer bias in TMA analysis. The results were analyzed using independent Student t-test, chi-square, log-rank regression, and Kaplan-Meier methods.

RESULTS:

One hundred sixteen patients were identified for complete analysis, and 56 patients had complete survival data. Median follow-up for survivors was 14.5 mo. Total cellular levels of ADM2 were found to be a predictor of survival in pancreatic cancer. Low ADM2 levels were associated with a higher 5-y survival compared with high ADM2 levels (18% versus 6%, P = 0.05). Median survival was also worse in high ADM2 expressers (18.7 versus 8.6 mo). In accordance with prior-published pancreatic cancer data, a worse histologic grade (P = 0.001), tumor (T) stage (P = 0.009), and overall disease stage (P = 0.004), all portended a worse survival.

CONCLUSIONS:

For the first time, we have demonstrated that high levels of ADM2 expression predict a poorer survival in patients with pancreatic adenocarcinoma. This suggests a possible role of ADM2 in pancreas cancer and as a novel biomarker that predicts poorer survival. Additional study of ADM2 in pancreatic cancer will help reveal its true angiogenic role in pancreas cancer and its potential role as a novel therapeutic target.

KEYWORDS:

Adrenomedullin-2; Biomarker; Intermedin; Pancreatic adenocarcinoma; Therapeutic target; Tissue microarray; Tumor angiogenesis

PMID:
25982376
DOI:
10.1016/j.jss.2014.11.002
[Indexed for MEDLINE]

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