Stanniocalcin 2 Expression In Cervical Cancer: Function Study And Clinical Significance

Introduction:Cervical cancer is the most common malignant tumor in the female reproductive system. Its morbidity and mortality both rank 4th among women cancers worldwide. Therefore, it becomes critical to develop a more sensitive and more effective biomarker in the clinical management of cervical cancer, which may assist diagnosis, guide treatment strategy, and predict therapeutic outcomes.Stanniocalcin 2 (STC2) is a glycoprotein hormone which expresses in a wide array of tissues and plays an important role in many physiological and pathological processes. STC2 has been proved by a number of studies, that it is closely related to the occurrence and development of some cancer. However, it remains unclear whether there is abnormal expression of STC2 in cervical cancer tissues, and whether STC2 is associated with cervical cancer pathological features, and whether it could predict radio-therapeutic outcomes in patients with cervical cancer. By analyzing data from clinical tumor samples and cervical cancer cell experimental models, and following-up patient survival after radiotherapy, we intended to study the clinical significance of STC2 expression in cervical cancer tissues and the correlation between STC2 expression levels and the proliferation, invasion and migration of cervical cancer cells, to evaluate whether STC2 can predict the radio-therapeutic effect in cervical cancer.Objective:To explore the expression level of STC2 in cervical cancer, evaluate the influence of STC2 expression on tumor cell function, and its clinical significance for the patients with cervical cancer.Methods:(1) Tumor samples from 50 patients with cervical cancer were collected. We detected the expression of STC2 mRNA by real-time PCR and the expression of STC2 protein by western blot in tumor tissues and corresponding adjacent normal tissues; and analyzed the correlation between STC2 expression and the clinicopathological features of these patients.(2) Si-STC2 was transfected into Hela cells, a well-established cervical cancer cell line, to silence the expression of STC2 in these cells. Western blot was performed to confirm the knockdown of STC2 protein in the transfected cells. The cell multiplication efficiency was analyzed by CCK-8 assay, the cell invasive ability by transwell assay, and the cell migration ability by cell wound scratch assay.(3) Tumor samples from 92 patients with cervical cancer who were diagnosed and treated from 2004 to 2007 were collected, with clinic-pathological parameters of each case recorded, and followed-up for about 5 years after the initiation of radiation therapy. Expression of STC2 mRNA and protein were detected. The correlation between STC2 expression and the clinicopathological parameters, and the overall survival and progression free survival of the patients were analyzed. Multivariate regression analysis was performed with the Cox proportional hazards regression model to analyze the independent factors related to prognosis.Result:(1) The expression of STC2 mRNA and protein in cervical cancer tissues was significantly higher than its expression in normal tissues. The expression of STC2 is irrelevant to age, FIGO stage, tumor size, differentiation, histology, but related to lymphatic metastasis (P=0.002<0.01)(2) After silencing STC2 expression, the multiplication, invasion and migration ability of Hela cells were decreased.(3) In contrast to low levels of STC2 expression, high levels of STC2 expression was correlated with shorter OS (P=0.013<0.05) and shorter PFS (P=0.004<0.01) in patients with cervical caner after radiotherapy. Moreover, lymph node metastasis was found to be correlated with shorter OS (P=0.035<0.05)Conclusion:(1) The expression of STC2 in cervical cancer tissues was significantly higher than its expression in corresponding adjacent normal tissues;(2) STC2 promotes the proliferation, invasion and metastasis of cervical cancer Hela cells;(3) The expression of STC2 was related to lymphatic metastasis;(4) The expression of STC2 was significantly and inversely correlated with OS and PFS in patients with cervical cancer.