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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

ORGANISM(S): Homo sapiens

PROVIDER: GSE11127 | GEO | 2010/02/15

SECONDARY ACCESSION(S): PRJNA106909

REPOSITORIES: GEO

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Project description:BACKGROUND; Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is around 50% and tumor derived molecular prognostic markers are needed for estimation of response and survival. METHODS; Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes having an expression with high correlation to survival time after chemotherapy was identified. Two of these genes were selected for validation by immunohistochemistry (IHC) in tumor tissue from 149 cisplatin treated patients having complete follow-up data. RESULTS; Fifty-five differentially expressed genes correlated significantly to survival time. Two of these (Emmprin and Survivin) were validated using IHC, and multivariate analysis (n=145) identified Emmprin expression (hazard ratio 2.38; p<0.0001) and Survivin expression (hazard ratio 2.34; p<0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio 2.72; p<0.0001). In the good prognosis group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (p<0.0001). Within this group of patients, the subgroups of patients with no positive, one positive or two positive IHC stainings (Emmprin and Survivin) had estimated 5-year survival rates (+- SE) of 35.6+-?%, 6.3+-?%, and 0+?%, respectively. Response to chemotherapy could also be predicted with an OddsRatio of 4.60 (2.13-9.93) and 2.59 (1.25-5.38) for Emmprin and Survivin respectively. CONCLUSION; Emmprin and Survivin proteins were identified as strong independent prognostic predictors for response and survival after cisplatin-containing chemotherapy in patients with bladder cancer. Experiment Overall Design: Tumors from 30 patients with advanced bladder cancer used in the study. A SAM analysis was used for identifying genes co-varying with treatment response.

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

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