The significance of NTR1 expression and its correlation with β-catenin and EGFR in gastric cancer

Abstract

Background: Several reports indicate the high-affinity receptor of NT (neurotensin), NTR1 (neurotensin receptor 1), in numerous detrimental functions linked to neoplastic progression of several cancer types. Recently, it has also been shown that NTR1 gene is a target of the Wnt/APC oncogenic pathways connected with the β-catenin/Tcf transcriptional complex and NT can stimulate cancer proliferation in an EGFR-dependent mechanism. In this study, we explored NTR1, β-catenin and EGFR expression in gastric cancer. The possible associations of NTR1 expression with clinicopathological factors, prognosis, β-catenin and EGFR were analyzed. Methods: NTR1, β-catenin and EGFR expression in gastric cancer tissues and the adjacent normal tissues of 210 cases was detected by Immunohistochemistry. The possible associations of NTR1 expression with clinicopathological data, prognosis, β-catenin and EGFR were analyzed. Results: 1. NTR1 expression in tumor tissues was significantly higher than that in adjacent normal tissues (P <0 .01). 2. Its expression was positively correlated with pathological grade, T stage, N stage and TNM stage and was not correlated with sex, age, tumor size and Lauren's classification. 3. A co-expression of NTR1 and nuclear β-catenin was in 53 (25.2 %) of cases and NTR1 expression was positively correlated with β-catenin nuclear translocation. NTR1 expression was not correlated with EGFR expression, but at a critical value (P = 0.05). 4. By log-rank test, higher expression of NTR1, higher pathological grade, diffusion Lauren's classification and advanced TNM stage showed worse prognosis (P <0 .05). Age, sex, tumor size, β-catenin and EGFR had no prognostic significance. Multivariate Cox analysis showed that NTR1 expression and TNM clinical stage (P <0 .05) were the independent prognostic factors for patients with GC. Conclusion: By immunohistochemistry, we found that a high expression of NTR1 in GC specimens, which showed a bad prognosis, besides, NTR1 expression was related to invasion and migration of GC. These findings provide new and important information on the progression of GC. This study indicated that NTR1 may play an important role in tumor progression of GC and have its potential to be a predictive biomarker or a therapeutic molecular target in GC. The interaction between NTR1 and β-catenin may participate in the development of GC. However, the relationship between NTR1 and EGFR needs to be further investigated.