Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological malignancies. Topotecan remains an essential tool in second-line therapy; even so, most patients develop resistance within a short period of time. We aimed to identify biomarkers of topotecan resistance by using gene expression signatures derived from patient specimens at surgery and available subsequent responses to therapy. Gene expression was collected for 1436 patients and 10,103 genes. Based on disease progression, patients were categorized as responders/nonresponders depending on their progression free survival (PFS) state at 9, 12, 15 and 18 months after surgery. For each gene, the median expression was compared between responders and nonresponders for two treatment regimens (chemotherapy including/excluding topotecan) with Mann-Whitney U test at each of the four different PFS cutoffs. Statistical significance was accepted in the case of p < 0.05 with a fold change (FC) 1.44. Four genes (EPB41L2, HLA-DQB1, LTF and SFRP1) were consistently overexpressed across multiple PFS cutoff times in initial tumor samples of patients with disease progression following topotecan treatment. A common theme linked to topotecan resistance was altered immune modulation. Genes associated with disease progression after systemic chemotherapy emphasize the role of the initial organization of the tumor microenvironment in therapy resistance. Our results uncover biomarkers with potential utility for patient stratification

Állami támogatások számviteli elszámolása és hatása az eredményre

An essential tool for the economic activity and the rural development are the system of state subsidies. The non-refundable subsidies given for development goals enable the development of businesses on the long term, while the non-refundable subsidies, given for covering of the costs, help to solve the daily liquidity problems and improve their profit generating activity. The accounting of the national subsidies requires specific professional skills from the enterprise. Beside the regulatory compliance accounting can have concrete results and tax consequences. A separate problem in case of the non-refundable subsidies connected to development is the accounting of the amortization. According to the general regulation the accounting of the amortization (accruals) is appropriate, however the accounting of non-refundable subsidies for development placed to the capital reserves (restricted reserves) reveal a serious economic contradiction in the assets and liabilities