Overexpression of human chorionic gonadotropin beta genes 3, 5 and 8 in tumor tissue and urinary cells of bladder cancer patients.
OBJECTIVE
Human chorionic gonadotropin (hCG) is a marker of trophoblastic tumors, and the serum concentration of the free beta-subunit (hCGbeta) is an independent prognostic marker in several nontrophoblastic cancers. hCGbeta is encoded by six genes, of which the type II genes (hCGbeta 3/9, 5 and 8) are thought to be upregulated in relation to type I genes (hCGbeta 6/7) in cancer.


METHODS
We developed a novel quantitative RT-PCR method for the quantification of the relative expression levels of the two groups of hCGbeta genes and analyzed 28 bladder tumors and 15 urine samples.


RESULTS
We found a higher relative expression level of type II genes in malignant compared with benign urothelia (p = 0.016) and in exfoliated urinary cells from cancer patients compared with those from benign controls (p = 0.026). The expression level was increasing with higher stage (p = 0.014) and grade (p = 0.001) and tended to be higher in relapsing tumors (p = 0.059).


CONCLUSIONS
The increased hCGbeta concentrations in body fluids of patients with aggressive bladder cancer may be due to overexpression of type II genes. Quantification of the relative mRNA expression levels of the hCGbeta type I and II genes in urine cells should be further studied as a potential noninvasive tool for the diagnosis and follow-up of bladder cancer.
Hotakainen
Kristina
K
Department of Clinical Chemistry, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
Lintula
Susanna
S
Jarvinen
Riikka
R
Paju
Annukka
A
Stenman
Jakob
J
Rintala
Erkki
E
Stenman
Ulf-Håkan
UH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014556:Urine / Q000166:cytology
D014408:Biomarkers, Tumor; D018997:Chorionic Gonadotropin, beta Subunit, Human; D004273:DNA, Neoplasm; D012333:RNA, Messenger