Bettuzzi S, Davalli P, Astancolle S, Carani C, Madeo B, Tampieri A, Corti A
Department of Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy.
Cancer Res. 2000 Jan 1;60(1):28-34.
Using Northern blotting, the expression levels of the genes for polyamine metabolism regulatory proteins and clusterin have been measured in a series of 23 human prostate cancers (CaPs) dissected from radical prostatectomy specimens. Patient matched, nontumor tissue was dissected from benign areas of the gland. The results indicate that transcripts encoding ornithine decarboxylase (ODC), ODC antizyme, adenosylmethionine decarboxylase, and spermidine/spermine N1-acetyltransferase (SSAT) were significantly higher, whereas clusterin (sulfated glycoprotein 2) mRNA was significantly lower in tumors compared with the benign tissue. All mRNA levels were compared with those of histone H3 and growth arrest-specific gene 1, markers of cell proliferation and cell quiescence, respectively, and glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene. In poorly differentiated and locally invasive CaPs and in tumors with unfavorable prognosis or total prostate-specific antigen (PSA) levels > 10.0 ng/ml at diagnosis, an overall increase in the levels of H3 mRNA and a decrease in growth arrest-specific gene 1 mRNA was detected, indicative of higher proliferation activity, whereas the differences in expression levels for the polyamine metabolism and clusterin genes were higher. ODC and SSAT changes were positively correlated in normal tissue but not in high-grade cancer, whereas ODC antizyme and SSAT changes were positively correlated in more malignant CaPs but not in normal tissue. Tumor classification based on the changes in expression levels of all of the genes studied could be correlated to differentiation grade and local invasiveness classification systems in 72.2 and 83.3% of the cases, respectively. In a 1-year follow-up period, three patients whose CaPs ranked as less aggressive according to clinical staging, but classified as advanced cancers with the proposed molecular classification, showed increases in total PSA levels, indicative of tumor relapse. Thus, molecular classification, based on gene expression, may enhance the available prognostic tools for prostate tumors.
运用Northern印迹法，对一系列从根治性前列腺切除术标本中分离出的23例人类前列腺癌（CaP）中多胺代谢调节蛋白和簇集素基因的表达水平进行了测定。从腺体的良性区域分离出与患者匹配的非肿瘤组织。结果表明，与良性组织相比，肿瘤中编码鸟氨酸脱羧酶（ODC）、ODC反义酶、腺苷甲硫氨酸脱羧酶和亚精胺/精胺N1 - 乙酰转移酶（SSAT）的转录本显著更高，而簇集素（硫酸化糖蛋白2）mRNA显著更低。所有mRNA水平分别与组蛋白H3和生长停滞特异性基因1（细胞增殖和细胞静止的标志物）以及甘油醛 - 3 - 磷酸脱氢酶（一个管家基因）的水平进行了比较。在低分化和局部侵袭性CaP以及诊断时预后不良或总前列腺特异性抗原（PSA）水平>10.0 ng/ml的肿瘤中，检测到H3 mRNA水平总体升高，生长停滞特异性基因1 mRNA水平降低，表明增殖活性更高，而多胺代谢和簇集素基因的表达水平差异更大。ODC和SSAT的变化在正常组织中呈正相关，但在高级别癌症中并非如此，而ODC反义酶和SSAT的变化在恶性程度更高的CaP中呈正相关，但在正常组织中并非如此。基于所研究的所有基因表达水平变化的肿瘤分类，分别在72.2%和83.3%的病例中可与分化程度和局部侵袭性分类系统相关。在1年的随访期内，3例根据临床分期被列为侵袭性较低但根据所提议的分子分类被归类为晚期癌症的CaP患者，总PSA水平升高，表明肿瘤复发。因此，基于基因表达的分子分类可能会增强前列腺肿瘤现有的预后评估工具。
