The relationship between the preoperative plasma level of HIF-1α and clinic pathological features, prognosis in non-small cell lung cancer.

Jiabei He,Baolan Li,Siyi Zhang,Ying Hu,Mingming Hu

doi:10.1038/srep20586

Abstract

Studies have found that hypoxia is the most common feature in all of solid tumor progression, thus it has become a central issue in tumor physiology and cancer treatment. Hypoxia-inducible factor-1α (HIF-1α) could make the tumor produce adaptive biological response to hypoxia and become more aggressive. In this paper, we used enzyme linked immune sorbent assay to detect the plasma level of HIF-1α in patients with NSCLC and healthy volunteers. The results indicated that the 5-year survival rate of patients with squamous cell carcinomas is negatively correlated with the plasma level of HIF-1α and the 5-year survival rate of patients with low level of HIF-1α is higher than those with high level of HIF-1α. The plasma level of HIF-1α in patients with NSCLC is significantly higher than healthy volunteers. There is no significant correlation between the plasma level of HIF-1α and clinical features of NSCLC patients. In a word, there is no connection between the plasma level of HIF-1α and the clinical features of NSCLC patients as well as their prognosis. In stratified analysis, the plasma level of HIF-1α in patients with squamous cell carcinoma is associated with regional lymph node status.

Highlights

At Present, lung cancer is the leading cause of cancer-related deaths worldwide[1]
Several studies had found that the possible reasons for the adaptability response may as follows: In the process of tumor growth, when the blood supply could not meet the needs of the tumor growth, Hypoxia-inducible factor-1α (HIF-1α) would be activated by the hypoxia within the tumor, a series of HIF-1α dependent genes activated, regulating the biological characteristics of tumor from multiple pathways, so that the adaptive changes happened[10,11]
More than one hundred kinds of target genes associated with tumor growth and metastasis can be regulated and activated by HIF-1α, most of them were related to tumor progression and metastasis, such as gene involved in angiogenesis (VEGF, PDGF, PIGF), extracellular matrix degradation gene (MMPs), metastatic gene(SDF1, CXCR4, LOX), epithelial-mesenchymal transition gene (SNAIL, SIP) and so on[12]

Summary

Results

The relationship between the plasma level of HIF-1α and the clinical features (age, sex, histological type, tumor differentiation grade, T stage, local lymph node status, pTNM stage, tumor size and smoking condition) of patient with NSCLC was analyzed respectively. The 1-, 3- and 5-year postoperative survival rate of patients with NSCLC were 91%, 69%, 59% respectively, and not correlated with the plasma level of HIF-1α , age, gender, tumor differentiation grade, diameter of tumor and smoking status (P > 0.05). There was a significant relationship between 5-year postoperative survival rate of patients with squamous cell carcinomas and the plasma level of HIF-1α. There was no significant relationship between the 5-year postoperative survival rate and the plasma level of HIF-1α in patients with adenocarcinoma (Table 6). PTNM stage (P = 0.002) and the plasma level of HIF-1α (P = 0.028) were independent prognostic factors of patients with squamous cell carcinomas.

Discussion

No history of other cancers

Methods