The co-expression of ERβ2 and IL-12Rβ2 is better prognostic factor in non-small-cell lung cancer progression

Abstract

Estrogens and IL-12 play a pivotal role in the development and progression of non-small-cell lung cancer (NSCLC); at the same time, estrogen receptor β2 and (interleukin-12 receptor β2)IL-12Rβ2 are their important receptors, respectively. With the functions of ERβ2 and IL-12Rβ2 explored further in NSCLC, some questions on the relation between ERβ2 and IL-12Rβ2 expression need to be solved. In this study, our aim is to elucidate relationship and roles of ERβ2 and IL-12Rβ2 in NSCLC. The expression of estrogen receptors β2 and IL-12Rβ2 was confirmed by Western blot and RT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics was evaluated by Mann-Whitney and Kruskal-Wallis test. Using Kaplan-Meier plots and Cox proportional hazard models analyses, overall survival (OS) was evaluated. In contrast to benign pulmonary, ERβ2 and IL-12Rβ2 were over-expressed in NSCLC (p = 0.000). IHC results showed significant correlation between ERβ2 and IL-12Rβ2 (R = 0.382, p = 0.005). By analyzing the relation between ERβ2, IL-12Rβ2 mRNA expression levels and clinical characteristics, it was revealed that ERβ2 and IL-12Rβ2 were significant correlated with regional lymph node metastasis, T stage and clinical stage (p = 0.000/0.000; 0.001/0.000; 0.031/0.003 respectively), and both protein expression levels were lower with TNM stage being higher. In a Kaplan-Meier analysis, compared to both ERβ2 and IL-12Rβ2 or one low expression, high expression levels of ERβ2 and IL-12Rβ2 were identified in a group of patients with the longest overall survival (OS). Cox proportional hazard models revealed that ERβ2 and IL-12Rβ5 had longer OS. This is the first study to uncover that both ERβ2 and IL-12Rβ2 were over-expressed and further show that they were co-expressed in NSCLC. Moreover, we found that high expression levels of ERβ2 and IL-12Rβ2 may be positively correlated with OS and have prognostic values for the progression of NSCLC.