The oncogenetic role of stanniocalcin 1 in lung adenocarcinoma: a promising serum candidate biomarker for tracking lung adenocarcinoma progression.

Stanniocalcin 1 (STC1) is reported to functionally participate in the development of several cancers. However, the role of STC1 in the tumorigenesis and progression of lung adenocarcinoma remains to be fully elucidated. Here, we found that the average levels of serum STC1 were 5.47, 5.53, and 6.94 ng/mL (P = 0.0045) in the healthy subjects and patients with lung adenocarcinoma at tumor stages I-II and III-IV according to Union for International Cancer Control (UICC), respectively. Subsequently, the positive correlation between the STC1 expression level in lung adenocarcinoma tissues and tumor stages was confirmed by immunohistochemical staining assay. Additionally, studies in the STC1-overexpressing or STC1-silenced stable cell lines showed that STC1 increased cell proliferation by promoting G1/S transition in cell cycle progression via up-regulating cyclin B1 and cyclin E. Moreover, studies in the STC1-overexpressing or STC1-silenced stable cell lines also showed that STC1 inhibited cell apoptosis by up-regulating the expression of anti-apoptosis proteins Bcl-2 and Bcl-xl and down-regulating the expression of pro-apoptosis proteins Bax, Bak, and Bid via the activation of the ERK and JNK signaling pathway. In addition, neutralization of STC1 with monoclonal antibody significantly increased the apoptosis of A549 cells. Taken together, our findings strongly suggest that elevated expression of STC1 protein at the III-IV stage of lung adenocarcinoma promotes tumorigenesis of lung adenocarcinoma and positively associates with the cancer progression, which may be of potential value as tumor marker in clinical tracking lung adenocarcinoma progression.