Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases.
OBJECTIVE
We examined whether RNA expression of CD133, a surface molecule expressed on progenitors from hematopoietic and endothelial lineages, and CD146, a pan-endothelial marker, are increased in the blood of cancer patients and whether these factors correlate with patient characteristics and are predictive factors of survival.


METHODS
We developed a real-time quantification method (nuclear acid sequence-based amplification) to determine expression of CD146 and CD133 mRNA in the peripheral blood mononuclear cells of 131 progressive cancer patients, 37 healthy volunteers, and 5 patients who received granulocyte colony-stimulating factor. Overall survival and other clinicopathologic variables were obtained. Cox proportional hazards studies were done.


RESULTS
We show that patients with metastatic disease have a significant increase in CD133 mRNA (P = 0.03), specifically patients with bone metastasis (P < 0.001). Cancer patients with high CD133 mRNA expression, using a defined cutoff value, show a decreased survival compared with patients with low or undetectable CD133 expression (21% versus 45% cumulative survival, respectively, after 20 months; P = 0.01). Among patients with metastasis to the bone, cumulative survival was 22%, compared with 61% for patients with high or low CD133 levels (P = 0.004). Multivariate analysis showed that CD133 expression is an independent predictor for overall survival in patients with bone metastases. CD146 mRNA was not increased in patients with cancer, nor did it correlate with clinical variables or survival.


CONCLUSIONS
CD133, but not CD146, mRNA expression is increased in cancer patients with metastatic disease, specifically with bone metastasis. In addition, CD133 mRNA expression seems to be an independent prognostic factor for overall survival.
Mehra
Niven
N
Department of Medical Oncology and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Penning
Maarten
M
Maas
Jolanda
J
Beerepoot
Laurens V
LV
van Daal
Nancy
N
van Gils
Carla H
CH
Giles
Rachel H
RH
Voest
Emile E
EE
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D001859:Bone Neoplasms / Q000097:blood* / Q000235:genetics / Q000556:secondary*; D051929:CD146 Antigen / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D010455:Peptides / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D015203:Reproducibility of Results
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger