Increased expression of IRS-1 is associated with lymph node metastasis in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China, which is with characteristics of early cervical lymph node metastasis and high incidence rate of distant metastasis. Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that is encoded by the IRS-1 gene in humans, plays an important role in the development, progression, invasion and metastasis of tumors. The aim of the present study was to investigate the association between the expression of IRS-1 protein and clinicopathological characteristics in NPC by immunohistochemistry. The results showed that the expression level of IRS-1 was significant higher in NPC than that in the control nasopharyngeal epithelia (P = 0.042). The positive percentage of IRS-1 expression in NPC with lymph node metastasis was also significantly higher than those without lymph node metastasis (P = 0.008). Positive expression of IRS-1 was proved to be the independent predicted factor for lymph node metastasis of NPC (P = 0.025) regardless of age, gender, histological type and clinical stages by multivariate logistic regression analysis. In addition, results showed higher sensitivity and agreement rate of IRS-1 for predicting lymph node metastasis of NPC patients. Taken together, high expression of IRS-1 might be closely correlated with lymph node metastasis in NPC and positive expression of IRS-1 could be used as an independent biomarker for predicting lymph node metastasis of NPC.

Keywords: Insulin receptor substrate (IRS); biomarker; insulin receptor substrate 1 (IRS-1); metastasis; nasopharyngeal carcinoma (NPC).

Figure 1

Expression of IRS-1 in NPC and non-cancerous nasopharyngeal control tissue was detected by IHC. The expression of IRS-1 was detected by IHC using specific antibody as described in the section of materials and methods. Strong positive staining of IRS-1 was identified on the membrane and cytoplasm of NPC cells (A and B, 20×, IHC, AEC staining), also (A) showed positive staining IRS-1 on the membrane and cytoplasm in a small subset of lymphocytes infiltrating NPC tissues. Membrane and cytoplasm positive staining of IRS-1 was showed in the normal nasopharyngeal epithelial cells (C, 20×, IHC, AEC staining). Negative staining of IRS-1 in the NPC (D, 20×, IHC, AEC staining).

Figure 2

Kaplan-Meier overall survival curves of NPC patients with expression of IRS-1 and different clinicopathological characteristics. Kaplan-Meier analysis to plot the survival curve of 245 cases of NPC patients with expression of IRS-1 protein and clinicopathological characteristics and statistical significance were assessed using the log-rank test. A: Positive expression of IRS-1 had no significantly correlation with overall survival rates of NPC patients (P > 0.05, two sided). B: NPC patients with clinical stage III and IV were significantly related to poor prognosis compared to those patients with clinical stage I and II (P = 0.011, two sided). C: NPC patients with lymph node metastasis (LNM) were significantly related to poor prognosis compared to those patients without lymph node metastasis (P < 0.001, two sided). D: NPC patients with combination chemotherapy and radiotherapy were significantly related to good prognosis compared to patients with chemotherapy alone or radiotherapy alone (P = 0.016, two sided).