Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

HSD17B10, RPL8, IFITM2 and IFITM3 as predictive markers of response to chemotherapy in conventional osteosarcomas.

ABSTRACT: The aim of this study was to identify molecular markers able to classify osteosarcoma patients as good or poor responders before therapy. Methods: Gene expression profiling of 20 non-metastatic high-grade osteosarcoma patients was performed using cDNA nylon microarray which contained 8,032 unique sequenced-verified cDNA clones, representing 5,776 distinct genes. Expression of selected genes was validated using RTQ-PCR. For correlated genes, corresponding proteins were explored. Immunohistochemistry (IHC) on sections of tissue microarrays (TMA) were performed on a cohort of 50 patients, out of which 30 were new patients. Furthermore, fluorescent in situ hybridization (FISH) was performed on gene which could not be tested using IHC. Results: We have found that HSD17B10 gene expression was upregulated in the group of poor responders and that IHC expression of HSD17B10 in biopsy done before treatment was correlated to response to chemotherapy in 50 patients. Other relevant results include correlation of IFITM2, IFITM3 and RPL8 gene expression to response to chemotherapy. RPL8 gene expression also had a prognostic value for event-free survival. Moreover, a significant statistical correlation was found between polysomy 8 of RPL8 and good response to chemotherapy. Conclusion: These data suggest that HSD17B10 gene may be a biological marker and a therapeutic target in conventional osteosarcoma. This study highlights the prognostic and the predictive value of RPL8. RPL8 and IFITM2 may be useful in the assessment of patients with osteosarcoma at diagnosis and for stratifying patients taking part in randomized trials. Keywords: Gene-expression profiling Gene expression profiling of 20 non-metastatic high-grade osteosarcoma patients was performed using spotted cDNA nylon membrane

ORGANISM(S): Homo sapiens

SUBMITTER: Wilfried Gouraud

PROVIDER: E-GEOD-11127 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: predictive value of HSD17B10 and IFITM2.

Salas Sébastien S 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

International journal of cancer 20090801 4

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 nonmeta ...[more]

PMID: 19449377

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Project description:Background Currently, no gene-expression signature (GES) established from node-positive cohorts, able to predict breast cancer evolution after systemic adjuvant chemotherapy, exists. Methods Gene-expression profiles of 252 node-positive patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array representing 5,776 distinct genes. Findings In the training cohort, we established a 38-GES for the purpose of predicting time to distant metastasis. The 38-GES yielded unadjusted hazard ratio of 4.86 (95% CI=2.76-8.56). Even when adjusted with the two best clinicopathological prognostic scoring: NPI and Adjuvant!, 38-GES HR were 3.30 (1.81-5.99) and 3.40 (1.85-6.24), respectively. Furthermore, 38-GES improved mostly NPI and Adjuvant! intermediate-risk classified patients. NPI intermediate-risk patients (7-year MFS=87.2%) were divided into 2/3 (7-year MFS=95.5%) close to NPI low-risk group and 1/3 (7-year MFS=69.3%) close to NPI high-risk group (HR=6.97 [2.51-19.36]). Adjuvant! intermediate-risk patients (7-year MFS=88.0%) were divided into 2/3 (7-year MFS=94.8%) close to Adjuvant! low-risk group and 1/3 (7-year MFS=71.7%) close to Adjuvant! high-risk group (HR=5.31 [5.38-11.87]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts (n=224) generated from different microarray platforms. The 38-GES yielded unadjusted HR=2.95 (1.74-5.01). Furthermore, 38-GES showed performance in supplementary cohorts with different lymph-node status and endpoint (1,031 new patients). Interpretation The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and especially powerful to separate NPI or Adjuvant! intermediate-risk node-positive patients. Keywords: disease-state analysis 252 breast cancer patients at diagnosis examined with spotted cDNA nylon membrane. Patient details: PACS01x are 2 parts of a clinical trial : PACS01A : patients had received 6 cycles of FEC100 PACS01B : patients had received 3 cycles of FEC100 then 3 cycles of Docetaxel CCRG are patients from our local cancer center (Cancer Center René Gauducheau) included with the same criteria as PACS01A (6 cycles of FEC100).

Dataset Information

HSD17B10, RPL8, IFITM2 and IFITM3 as predictive markers of response to chemotherapy in conventional osteosarcomas.

Publications

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: predictive value of HSD17B10 and IFITM2.

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