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

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.