Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.
To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P<0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.
Ochi
Kensuke
K
Laboratory of Molecular Medicine and Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Daigo
Yataro
Y
Katagiri
Toyomasa
T
Nagayama
Satoshi
S
Tsunoda
Tatsuhiko
T
Myoui
Akira
A
Naka
Norifumi
N
Araki
Nobuto
N
Kudawara
Ikuo
I
Ieguchi
Makoto
M
Toyama
Yoshiaki
Y
Toguchida
Junya
J
Yoshikawa
Hideki
H
Nakamura
Yusuke
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002648:Child; D002945:Cisplatin / Q000494:pharmacology; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007069:Ifosfamide / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D015854:Up-Regulation
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018076:DNA, Complementary; D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide