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- W2243877812 abstract "20034 Background: Resistance to chemotherapy regimes is a critical problem in the clinical management of metastatic melanoma malignum resulting in a very short survival in the majority of patients. The biological mechanisms behind the therapy resistance are still unclear. The identification of survival and thereapy-specific dysregulated genes could identify new molecular markers. Patients and Methods: Twelve patients treated with malignant melanoma with known complete survival and chemotherapy data were enrolled in the study. All patients received cisplatin/carboplatin combination therapy. After surgery, the tissue samples were frozen, and RNA was isolated using the Qiagen RNeasy kit. Microarray analysis was performed using Affymetrix HGU133A chips. Before statistical analysis the genes exhibiting less than 50% present calls and genes with less than 10% having at least 1.5 fold intensity variations were excluded. Feature selection was performed using the Wald statistic, Cox proportional hazard model of the survival analysis in the BRB ArrayTools software package. Significance was set at p<0.05. For an in silico validation we used the key word “melanoma” and found one microarray study containing 83 microarrays and available raw data in GEO (GSE8401). The downloaded dataset was MAS5 normalized and SAM was performed setting the false discovery rate below 0.01. Results: Seven patients passed the quality criteria and were included in the study. All together 8207 genes passed the filtering criteria. 33 genes were associated with aggressiveness and 42 genes with survival after chemotherapy. Only PICALM (phosphatidylinositol binding clathrin assembly protein) was associated with both therapy response and survival. In GSE8401 3006 genes were significant to discriminate metastasis and primary melanomas. The overlap of the significant GSE8401 and the top 33 survival- associated genes contains 5 genes. The overlap of the significant GSE8401 and the top 42 chemoresponse-associated genes contains 11 genes. Conclusions: Our results demonstrate a high diversity of gene expression profiles associated with melanoma overall- and therapy survival. We provide new data that can be used to obtain further insight into the mechanisms of therapy response. No significant financial relationships to disclose." @default.
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- W2243877812 date "2008-05-20" @default.
- W2243877812 modified "2023-10-16" @default.
- W2243877812 title "Different gene sets correlated to overal and chemotherapy survival in human malignant melanoma" @default.
- W2243877812 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.20034" @default.
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