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

Dag Andre Nymoen,Ben Davidson,Thea E Hetland Falkenthal,Claes G Tropé,Arild Holth

doi:10.1186/s12943-015-0317-1

Dag Andre Nymoen, Ben Davidson + Show 3 more

Open Access

https://doi.org/10.1186/s12943-015-0317-1

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Journal: Molecular Cancer	Publication Date: Feb 18, 2015
Citations: 69	License type: CC BY 4.0

Affiliation: Oslo University Hospital, University of Oslo

Abstract

BackgroundThe 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.MethodsAdvanced-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.ResultsABCA4 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).ConclusionsOur 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.

Highlights

Ovarian cancer, consisting predominantly of ovarian carcinoma (OC), is the most lethal gynecologic malignancy, constituting the 5th and 4th most common cause for cancer-related death in women in the U.S and Norway, respectively [1,2]
Chemoresistance-associated genes are significantly related to clinicopathologic parameters Analysis of mRNA levels for the 14 studied genes in the 150 effusions identified several significant associations with anatomic site, patient age and residual disease volume (Table 3)
In analysis of post-chemotherapy effusions, only age was significantly associated with gene expression, with associations identified between older age and lower ABCA4 (p = 0.02) and higher BIRC6 (p = 0.03), ABCA13 (p = 0.008) and fatty acid synthase (FAS) (p = 0.018) levels

Summary

Introduction

Ovarian cancer, consisting predominantly of ovarian carcinoma (OC), is the most lethal gynecologic malignancy, constituting the 5th and 4th most common cause for cancer-related death in women in the U.S and Norway, respectively [1,2]. OC progresses predominantly within the abdominal cavity and to a lesser degree by metastasis to the pleural space, frequently with the formation of malignant effusions. We previously analyzed 32 serous OC effusions for the expression of 381 genes which have been reported to be associated with chemoresistance. 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

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