Expression and Significance of HIF-1α and HIF-2α in Pancreatic Cancer

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 35; no. 6; pp. 874 - 879
• Main Authors: Wang, Min, Chen, Mei-yuan, Guo, Xing-jun, Jiang, Jian-xin
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.12.2015; Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China%Department of Hepatic-biliary-pancreatic Surgery, Hubei Cancer Hospital, Wuhan 430079, China
• Subjects: Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; HIF-1α; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Medicine; Medicine & Public Health; mRNA; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Prognosis; RNA, Messenger - genetics; 临床病理; 免疫组化方法; 病理特征; 缺氧诱导因子-1α; 聚合酶链反应; 胰腺癌; pancreatic cancer; HIF-1α; HIF-2α; prognosis; aggressiveness
• ISSN: 1672-0733; 1993-1352; 1993-1352
• DOI: 10.1007/s11596-015-1521-3

Summary： The expression levels of hypoxia-inducible factor lalpha （HIF-lct） and HIF-2a in pancreatic cancer （PC） and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1 α and HIF-2α mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1 α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α mRNA was up-regulated in most cancer tis- sues （P〈0.05）. HIF-1α staining was weakly positive in most cancer tissues and strongly positive in ad- jacent pancreas tissues （P〈0.05）. Clinicopathologic analysis revealed that relatively strong HIF-1α ex- pression in cancer tissues was related to greater invasion （P〈0.05）, higher tumor pathologic stage （P〈0.05）, higher American Joint Committee on Cancer （AJCC） stage （P〈0.05） and shorter overall sur- vival time （P〈0.05）. Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion （P〈0.05）, lower tumor pathologic stage （P〈0.05）, lower AJCC stage （P〈0.05） and longer overall survival time （P〈0.05）. Moreover, the HIF-1αhigh/HIF-2αlow group showed a shorter survival time than the HIF-1αlow/HIF-2αhigh group. In con- clusion, although HIF-1α and HIF-2α mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.