Expression and clinical significance of insulin-like growth factor 1 in lung cancer tissues and perioperative circulation from patients with non-small-cell lung cancer.

S Fu,J Wang,Y Liao,C Liu,Y Deng,H Tang,X Fu,Q Xu

doi:10.3747/co.23.2669

Abstract

We explored the role of insulin-like growth factor 1 (igf-1) in the development of lung cancer. We used immunohistochemistry to measure the expression of igf-1 and igf-1 receptor (igf-1r) in specimens of tissue and perioperative circulation from 80 patients with primary non-small-cell lung cancer (nsclc) and from 45 patients with benign pulmonary lesions (bpls). Correlations of those measurements with clinicopathologic characteristics and clinical follow-up were analyzed. Circulating igf-1 was measured before and after surgery in all patients. Compared with bpl specimens, nsclc specimens showed overexpression of igf-1and igf-1r (p < 0.001). The expression levels of igf-1 and igf-1r were significantly associated with advanced-stage disease (p = 0.034 and 0.029 respectively) and lymph node metastasis (p = 0.012 and 0.017 respectively), and expression of igf-1 correlated with tumour differentiation and tumour diameter (p = 0.011 and 0.021 respectively). Specimens positive for igf-1 or igf-1r were significantly correlated with shorter patient survival (p = 0.0012 and 0.0016 respectively). After surgery, circulating igf-1 was significantly elevated in patients with bpl (p = 0.0346) and significantly lower in patients with nsclc (p = 0.0030), especially in those with advanced-stage disease, a larger tumour size, regional lymphoid node metastasis, or lesser differentiation (p = 0.0092, 0.0051, 0.0131, and p < 0.001 respectively). In nsclc, igf-1 and igf-1r are upregulated, and expression of those factors is correlated with tumour progression and prognosis in nsclc patients. Radical resection of nsclc can directly influence the serum concentration of igf-1. Autocrine/paracrine igf-1 might be playing an important role in the development of lung cancer.

Highlights

The growth hormone insulin-like growth factor 1 is produced primarily by the liver as an endocrine hormone; it is produced in target tissues in a paracrine/autocrine fashion[1]
The expression levels of igf-1 and igf-1r were significantly associated with advanced-stage disease (p = 0.034 and 0.029 respectively) and lymph node metastasis (p = 0.012 and 0.017 respectively), and expression of igf-1 correlated with tumour differentiation and tumour diameter (p = 0.011 and 0.021 respectively)
In nsclc, igf-1 and igf-1r are upregulated, and expression of those factors is correlated with tumour progression and prognosis in nsclc patients

Summary

Introduction

The growth hormone insulin-like growth factor 1 (igf-1) is produced primarily by the liver as an endocrine hormone; it is produced in target tissues in a paracrine/autocrine fashion[1]. In several studies, including earlier work by our group, the igf-1 signalling pathway was shown to play a critical role in the development of lung cancer[2,3,4,5,6,7]. Targeting igf-1 might help to achieve a favourable outcome in lung cancer patients, but few studies have looked at the expression of igf-1 in serum and tissue in non-small-cell lung cancer (nsclc) and at the significant role it might play in that disease. We found that circulating serum igf-1 was significantly higher in nsclc patients whose tumours were larger in size, indicating that igf-1 might exerts its effects by the paracrine/autocrine route[8]. The significance of circulating igf-1 in the development of nsclc is not clear, and few studies have assessed the circulating level of igf-1 in patients undergoing surgical treatment for an existing lung cancer[13]

Methods

Results

Discussion

Conclusion