Nymoen Dag Andre, Holth Arild, Hetland Falkenthal Thea E, Tropé Claes G, Davidson Ben
Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway.
Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310, Oslo, Norway.
Mol Cancer. 2015 Feb 18;14:44. doi: 10.1186/s12943-015-0317-1.
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.
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.
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).
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.
本研究的目的是调查14种基因的表达及其临床作用,这些基因先前在一小系列卵巢浆液性癌积液中显示与化疗反应和/或无进展生存期相关。
采用定量实时PCR分析150例晚期浆液性卵巢癌积液中AKR1C1、ABCA4、ABCA13、ABCB10、BIRC6、CASP9、CIAPIN1、FAS、MGMT、MUTYH、POLH、SRC、TBRKB和XPA的mRNA表达。研究mRNA表达与临床病理参数的相关性,包括化疗反应和生存期。
在整个队列中,ABCA4 mRNA表达与诊断时更好的(完全)化疗反应显著相关(p = 0.018),而在对58例接受标准化疗(卡铂+紫杉醇)的化疗前积液患者的分析中,较高的POLH mRNA水平与诊断时更好的化疗反应显著相关(p = 0.023)。在化疗前积液患者(n = 77)的单因素生存分析中,CIAPIN1 mRNA表达与较短的总生存期(p = 0.007)和无进展生存期(p = 0.038)显著相关,而ABCA13 mRNA表达与较短的总生存期(p = 0.024)显著相关。在Cox多因素分析中,较高的CIAPIN1 mRNA表达是总生存期差的独立标志物(p = 0.044)。
我们的数据确定ABCA4和POLH为转移性浆液性癌中化疗反应较好的标志物。CIAPIN1和ABCA13可能是化疗前浆液性癌积液中预后不良的新标志物。