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.