Clinicopathological and prognostic significance of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma: a meta-analysis

Abstract

Published literatures on the prognostic value of hypoxia-inducible factor-1α (HIF-1α) overexpression in esophageal squamous cell carcinoma (ESCC) are conflicting and heterogeneous. We performed a meta-analysis to more precisely evaluate the clinicopathological and prognostic value of HIF-1α in patients with ESCC. Searches were applied to MEDLINE, Pubmed, Embase, Cochrane Library, Web of Science, and Chinese BioMedical Literature Databases until September 10, 2013, without language restrictions. The pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to estimate the effects. Twelve studies with 942 ESCC patients were selected to evaluate the correlation between HIF-1α and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC), and clinicopathological features. HIF-1α overexpression was significantly associated with poor OS (HR 1.78, 95% CI 1.41-2.24), DFS (HR 1.91, 95% CI 1.15-3.18), and RC (HR 3.56, 95% CI 1.68-7.53). Besides, HIF-1α overexpression was significantly associated with stage (OR 2.90, 95% CI 1.97-4.27), lymph node metastasis (OR 1.86, 95% CI 1.39-2.49), depth of invasion (OR 2.45, 95% CI 1.24-4.86), lymphatic invasion (OR 2.28, 95% CI 1.46-3.56), distant metastasis (OR 2.04, 95% CI 1.19-3.50), and vascular endothelial growth factor (OR 3.67, 95% CI 1.81-7.46). Our results indicate that HIF-1α overexpression can potently predict the poor prognosis and chemoradiation resistance for ESCC. Large prospective studies with multivariable survival analyses are now needed to confirm the clinical utility of HIF-1α as an independent prognostic marker.

Hypoxic control of metastasis

“…Immunohistochemical analysis of human primary tumor samples has revealed an association between high HIF-1 expression and metastasis in patients with gynecological, pancreatic, esophageal, lung, and prostate cancers ( 36–38 ). HIF-2 expression in primary tumors is also associated with distant metastasis in patients with small cell lung and breast cancers ( 39, 40 ).…”

Feasibility and repeatability of PET with the hypoxia tracer [18F]HX4 in oesophageal and pancreatic cancer

“…The pancreatic tumour microenvironment is characterized by hypoxia, resulting from an abundance of stromal tissue and reduced vascularization [8][9][10]. Several studies have shown the relation of tumour hypoxia with adverse outcome in both oesophageal [11] and pancreatic cancer [12]. Hypoxia driven cell preserving pathways are associated with a more aggressive and metastatic tumour phenotype as well as resistance to chemotherapy and radiation [13][14][15][16].…”

Novel Candidate Biomarkers of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma: A Systematic Review

“…Recently published studies on the prognostic value of HIF-1α overexpression in ESCC are conflicting and heterogeneous. However, Ping et al [46] performed a meta-analysis that included 12 studies with a total of 942 ESCC patients and found that HIF-1α overexpression was a potent predictor of a poor prognosis and resistance to CRT in ESCC. At present, HIF-1α appears to be one of the most promising candidate markers predictive of the response to CRT in ESCC.…”

“…We found meta-analyses that analyzed 12 studies of HIF-1α that included a total of 942 patients [46] and 28 studies of p53 that included a total of 1,497 patients [65]. At present, HIF-1α and p53 appear to be the most promising candidate biomarkers predictive of chemoradiosensitivity in ESCC.…”

“…However, for even these candidate biomarkers to be useful in clinical application, additional strong evidence of their efficacy will be required. For example, HIF-1α overexpression was significantly associated with poor OS and DFS, and with a poor response to CRT in a meta-analysis [46]. However, HIF-1α overexpression was also significantly associated with stage, lymph node metastasis, depth of invasion, lymphatic invasion and distant metastasis, and it is to be expected that more advanced ESCCs are related to a poor outcome and poor response to CRT.…”