Jung-A Choi

Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer

AbstractBackgroundMalignant ascites contributes to the metastatic process by facilitating the multifocal dissemination of ovarian tumour cells onto the peritoneal surface. However, the prognostic and diagnostic relevance of ascitic fluid remains largely unknown. Herein, we investigated the potential clinical value and therapeutic utility of ascitic autotaxin (ATX) in epithelial ovarian cancer (EOC).MethodsATX expression was assessed in clinical samples. Spheroid-forming assay, real-time PCR, western blot analysis, invadopodia assay, and adhesion assays were performed.ResultsAscitic ATX expression was highly elevated in patients with ovarian cancer compared to those with benign ascites and was associated with advanced stage, high grade, and a short disease-free period in patients with EOC. Combining the diagnostic ability of ascitic ATX and serum CA-125 levels significantly improved the area under the curve (AUC) value for EOC compared to serum CA125 level alone. This marker combination showed a large odds ratio for short disease-free period in high-risk EOC groups. Functional studies revealed that ascitic ATX was required for maintaining cancer stem cell-like characteristics and invadopodia formation.ConclusionAscitic ATX levels may serve as a useful prognostic indicator for predicting aggressive behaviour in EOC. ATX-linked invadopodia are a potential target to prevent peritoneal dissemination in ovarian cancer.

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.

Cervical Cancer Prevention Education Program for Rural Korean Immigrant Women

The study aimed to evaluate the effectiveness of a cervical cancer prevention education program for rural Korean immigrant women. A total of 46 Korean immigrant women who had not been screened in the past three years participated. The experimental group participated in the intervention program once a week for four weeks and completed a post-program survey in week 12. Compared to the control group, significant increases were detected in level of knowledge of cervical cancer prevention ( p = .001), behavioral attitude toward cervical cancer prevention ( p = .029) and behavioral intention regarding cervical cancer prevention ( p = .005) in the experimental group. Pap screening rate of the experimental group was significantly increased ( p = .029), but the rate of change in the selection of primary care providers was not significant. The results suggest the need for a multilevel approach to address cultural and systemic barriers to Korean immigrant women in promotion of cervical cancer prevention behavior.