CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma

Abstract

Background: The objective of this study was to investigate the expression and clinical role of 14 genes previously shown to be associated with chemotherapy response and/or progression-free survival in a smaller series of ovarian serous carcinoma effusions.

Methods: Advanced-stage serous ovarian carcinoma effusions (n = 150) were analyzed for mRNA expression of AKR1C1, ABCA4, ABCA13, ABCB10, BIRC6, CASP9, CIAPIN1, FAS, MGMT, MUTYH, POLH, SRC, TBRKB and XPA using quantitative real-time PCR. mRNA expression was studied for association with clinicopathologic parameters, including chemotherapy response and survival.

Results: ABCA4 mRNA expression was significantly related to better (complete) chemotherapy response at diagnosis in the entire cohort (p = 0.018), whereas higher POLH mRNA levels were significantly related to better chemoresponse at diagnosis in analysis to 58 patients with pre-chemotherapy effusions treated with standard chemotherapy (carboplatin + paclitaxel; p = 0.023). In univariate survival analysis for patients with pre-chemotherapy effusions (n = 77), CIAPIN1 mRNA expression was significantly related to shorter overall (p = 0.007) and progression-free (p = 0.038) survival, whereas ABCA13 mRNA expression was significantly related to shorter OS (p = 0.024). Higher CIAPIN1 mRNA expression was an independent marker of poor overall survival in Cox multivariate analysis (p = 0.044).

Conclusions: Our data identify ABCA4 and POLH as markers of better chemotherapy response in metastatic serous carcinoma. CIAPIN1 and ABCA13 may be novel markers of poor outcome in pre-chemotherapy serous carcinoma effusions.

Figure 1

Ciapin1 protein expression by immunohistochemistry. (A-B) Diffuse Ciapin1 expression (>75% of tumor cells) in the cytoplasm of OC cells in 2 effusions; (C) Focal expression (<5%) in another specimen; (D) Nuclear localization of Ciapin1, an unusual finding in this series.

Figure 2

CIAPIN1 and ABCA13 mRNA expression is associated with shorter survival in serous ovarian carcinoma. A: Kaplan-Meier survival curve showing the association between CIAPIN1 mRNA expression in effusions and overall survival (OS) for patients with pre-chemotherapy primary diagnosis effusions (n = 77). Patients with effusions with higher-than-median expression (n = 36, dashed line) had a mean OS of 22 months vs. 40 months for patients whose effusions showed lower-than-median expression (n = 41, solid line; p = 0.007). B: Kaplan-Meier survival curve showing the association between CIAPIN1 mRNA expression in effusions and progression-free survival (PFS) for patients with pre-chemotherapy primary diagnosis effusions (n = 77). Patients with effusions with higher-than-median expression (n = 36, dashed line) had a mean PFS of 7 months vs. 11 months for patients whose effusions showed lower-than-median expression (n = 41, solid line; p = 0.038). C: Kaplan-Meier survival curve showing the association between ABCA13 mRNA expression in effusions and OS for patients with pre-chemotherapy primary diagnosis effusions (n = 77). Patients with effusions with higher-than-median expression (n = 36, dashed line) had a mean OS of 24 months vs. 39 months for patients whose effusions showed lower-than-median expression (n = 41, solid line; p = 0.024).