CDNA microarray gene expression analysis of B-cell chronic lymphocytic leukemia proposes potential new prognostic markers involved in lymphocyte trafficking.
Human cancer is characterized by complex molecular perturbations leading to variable clinical behavior, often even in single-disease entities. We performed a feasibility study systematically comparing large-scale gene expression profiles with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL). cDNA microarrays were employed to determine the expression levels of 1,024 selected genes in 54 peripheral blood lymphocyte samples obtained from patients with B-CLL. Statistical analyses were applied to correlate the expression profiles with a number of clinical parameters including patient survival and disease staging. We were able to identify genes whose expression levels significantly correlated with patient survival and/or with clinical staging. Most of these genes code either for cell adhesion molecules (L-selectin, integrin-beta2) or for factors inducing cell adhesion molecules (IL-1beta, IL-8, EGR1), suggesting that prognosis of this disease may be related to a defect in lymphocyte trafficking. This report demonstrates the feasibility of a systematic integration of large-scale gene expression profiles with clinical data as a general approach for dissecting human diseases.
Stratowa
C
C
Boehringer Ingelheim Austria, Exploratory Research, Dr. Boehringergasse 5-11, A-1121 Vienna, Austria. christian.stratowa@vie.boehringer-ingelheim.com
Löffler
G
G
Lichter
P
P
Stilgenbauer
S
S
Haberl
P
P
Schweifer
N
N
Döhner
H
H
Wilgenbus
K K
KK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018821:CD18 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D018076:DNA, Complementary / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D051766:Early Growth Response Protein 1; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D015448:Leukemia, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis
D018821:CD18 Antigens; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D014157:Transcription Factors; D019041:L-Selectin; D012313:RNA