Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis

Abstract

Abstract. The aim of this study was to assess the significance of expression of hypoxia-inducible factor-1α (HIF-1α) and associated proteins in pancreatic ductal adenocarcinoma (PDA) and their impact on prognosis. Expression of HIF-1α, vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), survivin, CD34 and Ki-67 and apoptotic cells was demonstrated by immunohistochemistry or TUNEL in 58 PDAs and 20 normal pancreatic tissue samples. Our results show positivity of HIF-1α, VEGF, Glut-1 and survivin in 70.7%, 77.6%, 67.2% and 84.5% of the patients with PDA, respectively, which is significantly higher than in the normal counterparts. Expression of HIF-1α correlated positively with VEGF and Glut-1 expression but not with survivin. Strong HIF-1α expression associated with decreased apoptotic index and increased intratumoral microvessel density. Higher HIF-1α, VEGF and Glut-1 expression significantly associated with advanced tumor stage and lymph node metastasis. Patients with high HIF-1α, VEGF and Glut-1 expressing tumors had a poorer overall survival. Furthermore, Cox regression analysis showed that HIF-1α is a prognostic marker of borderline significance while VEGF was important in predicting poor outcome. These results suggest that over-expression of HIF-1α may play an important role in cancer progression through upregulation of VEGF and Glut-1 in PDA patients. HIF-1α and VEGF are potential candidates for predicting survival.

HIF-3α Promotes Metastatic Phenotypes in Pancreatic Cancer by Transcriptional Regulation of the RhoC–ROCK1 Signaling Pathway

“…A correlation between hypoxia and pancreatic cancer has been recognized for a number of years (21), and a role for HIF-1a and HIF-2a in pancreatic cancer has previously been investigated (22,23). In this study, we showed that HIF-3a expression is stimulated to a greater extent than either HIF-1a or HIF-2a under hypoxic conditions in pancreatic cancer cells.…”

Up-Regulation of Krüppel-Like Factor 5 in Pancreatic Cancer Is Promoted by Interleukin-1β Signaling and Hypoxia-Inducible Factor-1α

“…In favor of this hypothesis are results from a recently published study demonstrating that KRAS activation promotes KLF5 up-regulation in human colon cancer (HCT116) cells (13). Moreover, because hypoxia-mediated and cytokine-mediated activation of the oncogenic transcription factor hypoxia-inducible factor-1α (HIF-1α) is frequently encountered in pancreatic tumors, we also hypothesized that the interleukin (IL)-1β system and/or HIF-1α may be involved in the regulation of KLF5 expression (14)(15)(16)(17)(18). We therefore sought to further define the expression and regulation of KLF5 in human pancreatic cancer cells to expand our knowledge on this particular transcription factor and to potentially reveal a novel molecular therapeutic target.…”

The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

“…In addition, it hampers the delivery of oxygen, causing hypoxia [11]. Such a hypoxic microenvironment diminishes sensitivity to chemotherapeutics and radiation and negatively impacts prognosis [12][13][14][15][16].…”