Molecular characterization of the response to chemotherapy in conventional osteosarcomas: predictive value of HSD17B10 and IFITM2.
The therapy regimen of high-grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high-grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT-PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up-regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlated to response to chemotherapy. Other results include correlation of IFITM2, IFITM3, and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8, IFITM2, and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials.
Salas
Sébastien
S
Service Oncologie Médicale, Hôpital de la Timone, Assistance Publique-Hopitaux de Marseille, Marseille, France. sebastien.salas@ap-hm.fr
Jézéquel
Pascal
P
Campion
Loic
L
Deville
Jean-Laurent
JL
Chibon
Frédéric
F
Bartoli
Catherine
C
Gentet
Jean-Claude
JC
Charbonnel
Catherine
C
Gouraud
Wilfried
W
Voutsinos-Porche
Brigitte
B
Brouchet
Anne
A
Duffaud
Florence
F
Figarella-Branger
Dominique
D
Bouvier
Corinne
C
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics; D015996:Survival Rate; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C080081:IFITM2 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C075184:ribosomal protein L8, rat; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human