Doolan Padraig, Clynes Martin, Kennedy Susan, Mehta Jai Prakash, Crown John, O'Driscoll Lorraine
National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
Breast Cancer Res Treat. 2008 May;109(2):359-65. doi: 10.1007/s10549-007-9643-3. Epub 2007 Jul 12.
Preferentially expressed antigen of melanoma (PRAME) has been described as a potential candidate for immunotherapeutic targeting. However, the prognostic and predictive relevance of PRAME in breast cancer has never been investigated. PRAME gene expression was evaluated in 103 breast tumour biopsies, using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Normal breast tissue was also analysed for comparative purposes. All qRT-PCRs were performed in triplicate. Kaplan-Meier survival curves, Chi-squared and Cox Regression analyses were used to identify associations between PRAME expression and patients' clinicopathological and survival data. PRAME mRNA was detected in approximately 53% of tumour specimens and 37% of normal breast specimens. Kaplan-Meier analysis showed expression of PRAME to correlate significantly with unfavourable disease outcome for patients, in terms of both their disease-free survival (p = 0.0004) and overall survival (OS) (p = 0.0052) times from diagnosis. Multivariate analysis indicated PRAME expression to be an independent prognostic factor for shortened disease-free survival (p = 0.026) and OS (p = 0.02). Furthermore, for patients who received adjuvant chemotherapy, significantly (p = 0.0291) shorter relapse-free survival was achieved for those whose tumour expressed PRAME, compared to those that did not express this transcript. Our results suggest that PRAME mRNA expression may be a useful prognostic and predictive marker for breast cancer.
黑色素瘤优先表达抗原(PRAME)已被描述为免疫治疗靶向的潜在候选物。然而,PRAME在乳腺癌中的预后和预测相关性从未被研究过。使用定量逆转录聚合酶链反应(qRT-PCR)在103例乳腺肿瘤活检组织中评估PRAME基因表达。为作比较,也对正常乳腺组织进行了分析。所有qRT-PCR均重复进行三次。采用Kaplan-Meier生存曲线、卡方检验和Cox回归分析来确定PRAME表达与患者临床病理及生存数据之间的关联。在约53%的肿瘤标本和37%的正常乳腺标本中检测到PRAME mRNA。Kaplan-Meier分析显示,就患者从诊断起的无病生存期(p = 0.0004)和总生存期(OS)(p = 0.0052)而言,PRAME的表达与患者不良疾病结局显著相关。多变量分析表明,PRAME表达是无病生存期缩短(p = 0.026)和总生存期缩短(p = 0.02)的独立预后因素。此外,对于接受辅助化疗的患者,与未表达该转录本的患者相比,肿瘤表达PRAME的患者无复发生存期显著缩短(p = 0.0291)。我们的结果表明,PRAME mRNA表达可能是乳腺癌一个有用的预后和预测标志物。