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

Abstract

Objective We explored the role of insulin-like growth factor 1 (igf-1) in the development of lung cancer. MethodsWe 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. ResultsCompared 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). ConclusionsIn 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.

Association between high expression of phosphorylated Akt and mammalian target of rapamycin and improved survival in salivary gland adenoid cystic carcinoma

“…Neither PI3K nor IGF‐1Rβ had an impact on patient survival in our series. Although IGF‐1R overexpression has been frequently reported in neoplasms, and PIK3CA mutation in addition with copy number gains and mRNA overexpression have been reported to be the highest percentage of mutations in malignancies, such as head and neck squamous cell carcinoma, they are not the major driving force for the Akt/mTOR pathway hyperactivation detected in salivary gland ACC according to our results. Moreover, PTEN is an inhibitor of the PI3K/Akt/mTOR pathway, and loss of PTEN expression has been observed in many solid tumors .…”

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

“…37 In addition, it was found that IGF-1 may induce lymphangiogenesis and facilitates lymphatic metastasis, 38 and be associated with larger tumor size, local LNM, and worse prognosis in cancers. 37 In addition, it was found that IGF-1 may induce lymphangiogenesis and facilitates lymphatic metastasis, 38 and be associated with larger tumor size, local LNM, and worse prognosis in cancers.…”

Recent updates on the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors and resistance reversion strategies in lung cancer

“…IGF1R is overexpressed in many cancers, including lung cancer, which results in poor prognosis at an early stage. 98 It has been observed that overexpressed IGF1R causes erlotinib resistance in NSCLC cells. 99 Moreover, downregulation of IGF1R by inhibiting survivin protein expression or mTOR-mediated protein synthesis further sensitizes resistant NSCLC cells to erlotinib.…”

“…The IGF1R is a TK receptor, abnormalities of which confer resistance to EGFR‐TKIs through the activation of EGFR bypass signaling, even in the presence of inhibitors. IGF1R is overexpressed in many cancers, including lung cancer, which results in poor prognosis at an early stage 98 . It has been observed that overexpressed IGF1R causes erlotinib resistance in NSCLC cells 99 .…”