Abstract
Background: The genetic control of tumour progression presents the opportunity for bioinformatics and gene expression data to be used as a basis for tumour grading. The development of a genetic signature based on microarray data allows for the development of personalised chemotherapeutic regimes. Method: ONCOMINE was utilised to create a genetic signature for ovarian serous adenocarcinoma and to compare the expression of genes between normal ovarian and cancerous cells. Ingenuity Pathways Analysis was also utilised to develop molecular pathways and observe interactions with exogenous molecules. Results: The gene signature demonstrated 98.6% predictive capability for the differentiation between borderline ovarian serous neoplasm and ovarian serous adenocarcinoma. The data demonstrated that many genes were related to angiogenesis. Thymidylate synthase, GLUT-3 and HSP90AA1 were related to tanespimycin sensitivity (p=0.005). Conclusions: Genetic profiling with the gene signature demonstrated potential for clinical use. The use of tanespimycin alongside overexpression of thymidylate synthase, GLUT-3 and HSP90AA1 is a novel consideration for ovarian cancer treatment.
Highlights
Key Features of Cancer Traditional theory states that cancer is a simple disease involving down-regulated control over cell proliferation
When the three genes significantly associated with the outcome of disease and controlling the expression of hypoxia inducible factor 1 beta (HIF-1β – alias ARNT), heat-shock protein 90 (HSP90AA1) and topoisomerase 2-α (TOP2α)) were utilised in an economical logistic regression, the predictive capability remained high at 95.9%, demonstrating the potential for the gene profiling of just three genes to predict disease staging
When the data relating to the genes is considered, it can be seen that hypoxia-inducible factor (HIF)-1β, HSP90AA1 and placental growth factor (PGF) were over-expressed in ovarian cancer compared to normal ovarian cell lines and all had a large impact on the outcome of disease state ( PGF was not significantly associated)
Summary
Key Features of Cancer Traditional theory states that cancer is a simple disease involving down-regulated control over cell proliferation. Proto-oncogene mutation can lead to the formation of oncogenes and increases the probability of tumourgenesis, especially since those involving the amplification of gene frequency, such as that caused by mutations or polymorphisms in the promoter regions of genes (Biondi et al 2000), can increase the expression of proteins involved in malignant progression (Chow, 2010). This is exemplified by a polymorphism in the promoter region of the PR gene, which increases its transcription and production of the hPR-B protein in endometrial cancer (De Vivo et al 2002). The use of tanespimycin alongside overexpression of thymidylate synthase, GLUT-3 and HSP90AA1 is a novel consideration for ovarian cancer treatment
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