Expression of Hypoxia-Inducible Factors in Different Stages of Pancreatic Tumor Progression

Jung Hwa Jung,Henri K Parson,Danuta Sosnowska,Aaron I Vinik,Jessica Weaver,Carolina M Casellini

doi:10.3390/reports3040030

Abstract

Background: Early diagnosis in pancreatic cancer is key for improving prognosis. Hypoxia plays a critical role in tumor progression. Thus, an evaluation of associations between pancreatic tumor progression and markers of hypoxia is needed. Methods: We assessed the expression of hypoxia-inducible factors (HIF-1α and HIF-2α) by immuno-histochemical staining from 29 subjects with the following: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumor (NET), and pancreatic ductal adenocarcinoma (PDAC) and compared it to the expression in non-tumor samples. Results: Expression of HIF-1α increased significantly from PanIN (3.01 ± 0.17) to IPMN (7.63 ± 0.18), NET (9.10 ± 0.23) and PDAC samples (11.06 ± 0.15, p < 0.0001). Similar findings were observed for HIF-2α (p < 0.0001)}. A strong correlation between HIF-1α and HIF-2α expression was demonstrated (R2 = 0.8408, p < 0.0001). Conclusions: This data suggest that HIF-1α and HIF-2α may play a role in the progression from PanIN through PDAC. Further studies are necessary to confirm these findings and determine the effect of HIFs abrogation on tumor progression that can lead to novel therapies.

Highlights

The diagnosis and treatment of pancreatic cancer is perhaps the most vexing of all carcinomas.We do not currently have a reliable means of screening, or early biomarkers and as a result, most are found on a CT/MRI scan at an advanced stage
The aim of this study was to investigate the potential role of hypoxia-inducible factors on the progression of premalignant lesions to adenocarcinomas of pancreas
We found that significantly higher expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in pancreatic ductal adenocarcinoma (PDAC), InIPMN

Summary

Introduction

The diagnosis and treatment of pancreatic cancer is perhaps the most vexing of all carcinomas.We do not currently have a reliable means of screening, or early biomarkers and as a result, most are found on a CT/MRI scan at an advanced stage. More than half of these pancreatic cancers are ductal adenocarcinomas that grow rapidly and are diagnosed at a late stage, for which the 5-year survival is 3% [1]. Future hopes may rest in a better understanding of the molecular biology of pancreatic tumor progression that can be applied to enable early diagnosis and treatment [2]. Hypoxia plays a critical role in tumor progression. Methods: We assessed the expression of hypoxia-inducible factors (HIF-1α and HIF-2α) by immuno-histochemical staining from 29 subjects with the following: pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumor (NET), and pancreatic ductal adenocarcinoma (PDAC). Results: Expression of HIF-1α increased significantly from PanIN (3.01 ± 0.17) to IPMN (7.63 ± 0.18), NET (9.10 ± 0.23) and PDAC samples (11.06 ± 0.15, p < 0.0001). Conclusions: This data suggest that HIF-1α and HIF-2α may play a role in the progression from PanIN through

Objectives

Methods

Discussion

Conclusion