Prevalence and prognostic and predictive relevance of PRAME in breast cancer

Prevalence and prognostic and predictive relevance of PRAME in breast cancer
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DOI:
10.1007/s10549-007-9643-3
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发表时间:
2008-05-01
影响因子:
3.8
通讯作者:
O'Driscoll, Lorraine
O'Driscoll, Lorraine
中科院分区:
医学2区
文献类型:
--
作者:
Doolan, Padraig;Clynes, Martin;O'Driscoll, Lorraine

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黑色素瘤优先表达抗原(PRAME)被认为是一种潜在的免疫治疗靶点。然而,PRAME在乳腺癌中的预后和预测相关性从未被研究过。应用定量逆转录聚合酶链式反应(qRT-PCR)检测103例乳腺肿瘤组织中PRAME基因的表达。正常的乳房组织也被分析用于比较目的。所有qRT-PCR均为一式三份。采用Kaplan-Meier生存曲线、卡方检验和Cox回归分析确定PRAME表达与患者的临床病理和生存资料之间的关系。在53%的肿瘤标本和37%的正常乳腺标本中检测到PRAME mRNA。卡普兰-迈耶分析表明,PRAME的表达与患者的不良疾病结局显著相关,无论是从诊断开始的无病生存期(p=0.0004)还是总生存期(OS)(p=0.0052)。多因素分析显示PRAME表达是缩短无病生存期(p=0.026)和OS(p=0.02)的独立预后因素。此外,对于接受辅助化疗的患者,与那些不表达该转录本的患者相比,那些表达PRAME的肿瘤患者的无复发生存期显著缩短(p=0.0291)。我们的结果提示,PRAME mRNA的表达可能是乳腺癌预后和预测的有用标记物。
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 similar to 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.