Manni A, Mauger D, Gimotty P, Badger B
Department of Medicine and Center for Biostatistics and Epidemiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Clin Cancer Res. 1996 Nov;2(11):1901-6.
Although considerable experimental evidence suggests an important role of polyamines in breast cancer biology, compelling supportive data in patients are lacking. To address this issue, we measured ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase, and spermidine/spermine acetyltransferase (the three key polyamine metabolic enzymes) in a cohort of 50 primary human breast cancers and related their levels of activity to disease-free survival and overall survival. The major finding of our study was that ODC activity level was a negative independent prognostic factor for both end points. With regard to overall survival, the adverse influence of ODC expression was superior even to that provided by the number of positive nodes. Furthermore, the statistical significance of the ODC effect on survival was enhanced when breast cancer-specific mortality was included in the analysis as opposed to death from any cause. In addition, high tumor ODC activity may predict a shorter time from recurrence to death, although this effect was of only borderline statistical significance. In summary, these results provide the first concrete evidence supporting the prognostic role of ODC in human breast cancer.
尽管大量实验证据表明多胺在乳腺癌生物学中发挥重要作用,但在患者中缺乏有力的支持性数据。为解决这一问题,我们检测了50例原发性人类乳腺癌患者体内的鸟氨酸脱羧酶(ODC)、S-腺苷甲硫氨酸脱羧酶和亚精胺/精胺-N1-乙酰基转移酶(三种关键的多胺代谢酶),并将它们的活性水平与无病生存期和总生存期相关联。我们研究的主要发现是,ODC活性水平是这两个终点的负性独立预后因素。就总生存期而言,ODC表达的不良影响甚至优于阳性淋巴结数量所提供的影响。此外,当分析中纳入乳腺癌特异性死亡率而非任何原因导致的死亡时,ODC对生存影响的统计学意义增强。另外,肿瘤ODC活性高可能预示着从复发到死亡的时间较短,尽管这一效应仅具有边缘统计学意义。总之,这些结果提供了首个支持ODC在人类乳腺癌中预后作用的具体证据。