Identification and validation of novel biomarker TRIM8 related to cervical cancer.

Background: Cervical cancer, as a common gynecological disease, endangers female health. Give the lack of effective biomarkers for the diagnosis and treatment of cervical cancer, this paper aims to analyze the Gene Expression Omnibus (GEO) data sets using comprehensive bioinformatics tools, and to identify biomarkers associated with the cancer in patient samples. Methods: The bioinformatics methods were used to extract genes related to cervical cancer from GSE39001, while the GEO2R online tool to elaborate on differentially expressed genes (DEGs) in normal and cancer samples, and to clarify related genes and functions. The results were verified by IHC, WB, CCK-8, clone formation and flow cytometry experiments. Results: A total of 2,859 DEGs were identified in the GEO microarray dataset. We extracted genes associated with both ubiquitination and autophagy from the key modules of weighted gene co-expression network analysis (WGCNA), and the analysis showed that TRIM8 was of great significance for the diagnosis and prognosis of cervical cancer. Besides, experimental validation showed the high TRIM8 expression in cervical cancer, as well as its involvement in the proliferation of cervical cancer cells. Conclusion: We identified a biomarker (TRIM8) that may be related to cervical cancer through a series of analyses on the GEO dataset. Experimental verification confirmed the inhibition of cervical cancer cells proliferation by lowering TRIM8 expression. Therefore, TRIM8 can be adopted as a new biomarker of cervical cancer to develop new therapeutic targets.

High expression of PYK2 is associated with poor prognosis and cancer progression in early-stage cervical carcinoma.

Proline-rich tyrosine kinase-2 (PYK2), also known as calcium dependent tyrosine kinase, regulates different signal transduction cascades that control cell proliferation, migration, and invasion. However, the role of PYK2 in cervical cancer remains to be elucidated. The current study retrospectively included 134 patients with cervical cancer from December 2007 to September 2014. PYK2 expression was detected in tissue microarray and cervical cancer cell lines. Statistical analysis was performed to evaluate its clinicopathological significance. Small interfering RNA (siRNA) was employed to suppress endogenous PYK2 expression in cervical cancer cells to observe the biological function. PYK2 expression was up-regulated in cervical cancer specimens compared with paired adjacent normal cervical tissue samples. Statistical analyses indicated that PYK2 expression might be an independent prognostic indicator for patients with early-stage cervical cancer. A nomogram model was constructed based on PYK2 expression and other clinicopathological risk factors, and it performed well in predicting patients survival. In cellular studies, down-regulation of PYK2 remarkably inhibited cellular proliferation, migration and invasion. PYK2 expression possessed the potential to serve as a novel prognostic marker in cervical cancer patients.

The Prognostic Significance Of Pretreatment Albumin/alkaline Phosphatase Ratio In Patients With Stage IB-IIA Cervical Cancer.

BACKGROUND: Pretreatment albumin/alkaline phosphatase ratio (AAPR) has been discussed about its prognostic value in several malignancies, whereas its role in cervical cancer remains unclear. In this study, we attempt to explore the prognostic significance of the AAPR in stage IB-IIA cervical cancer patients who underwent a radical hysterectomy. PATIENTS AND METHODS: A total of 230 cervical cancer patients were enrolled in this retrospective study. The threshold value of AAPR was determined by receiver operating characteristic (ROC) curve. Kaplan-Meier survival analysis and multivariate analysis were performed to identify independent prognostic predictors of disease-free survival (DFS) and overall survival (OS). RESULTS: The optimal cut-off value of the preoperative AAPR was 0.68. Patients with AAPR<0.68 showed obviously inferior OS and DFS than those with AAPR>0.68 according to Kaplan-Meier curves (DFS: P = 0.011; OS: P = 0.017). In multivariate analysis, the preoperative AAPR showed to be an independent predictive factor for disease-free survival (DFS: P = 0.015) and overall survival (OS: P = 0.019). Moreover, subgroup analysis revealed that the lower AAPR was correlated with worse prognosis in patients with histologic grade I-II; but in those with histologic grade III, there was no significant difference between the two groups. CONCLUSION: Preoperative AAPR was a potentially valuable prognostic index in stage IB-IIA cervical cancer patients. Further prospective studies are required to validate its prognostic value.