Abstract
BackgroundIn recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways.Design and MethodsWe analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS).ResultsThe KRT81 (rs3660) GG genotype was associated with an increased risk of neurological toxicity (P = 0.016), while patients with XPO5 (rs11077) AA or CC genotypes had a higher rate of bleomycin-associated pulmonary toxicity (P = 0.048). Both miR-SNPs emerged as independent factors in the multivariate analysis. The XPO5 AA and CC genotypes were also associated with a lower response rate (P = 0.036). XPO5 (P = 0.039) and TRBP (rs784567) (P = 0.022) genotypes emerged as prognostic markers for DFS, and XPO5 was also associated with OS (P = 0.033). In the multivariate analysis, only XPO5 emerged as an independent prognostic factor for DFS (HR: 2.622; 95%CI 1.039–6.620; P = 0.041). Given the influence of XPO5 and TRBP as individual markers, we then investigated the combined effect of these miR-SNPs. Patients with both the XPO5 AA/CC and TRBP TT/TC genotypes had the shortest DFS (P = 0.008) and OS (P = 0.008).ConclusionmiR-SNPs can add useful prognostic information on treatment-related toxicity and clinical outcome in Hodgkin lymphoma and can be used to identify patients likely to be chemoresistant or to relapse.
Highlights
Hodgkin lymphoma (HL) is a highly curable B-cell neoplasm characterized by the presence of a relatively small population of malignant tumor cells, known as Hodgkin/Reed-Sternberg (HRS) cells, in a non-neoplastic microenvironment [1]
First-line therapy consisted of ABVD in 52% of patients and MOPPABVD in 38%
TRBP and XPO5 miR-SNPs in combination Given the evidence for the influence of TRBP and XPO5 as individual markers, we investigated the combined effect of these miR-SNPs on disease-free survival (DFS) and overall survival (OS)
Summary
Hodgkin lymphoma (HL) is a highly curable B-cell neoplasm characterized by the presence of a relatively small population of malignant tumor cells, known as Hodgkin/Reed-Sternberg (HRS) cells, in a non-neoplastic microenvironment [1]. As the neoplastic HRS cells typically represent ,1% of the total infiltrate, crosstalk between the non-neoplastic inflammatory cell infiltrate and the HRS cells is an integral and important aspect of HL[2]. The treatment of patients with HL is primarily guided by the clinical stage of disease. Stage I–II patients are treated with chemotherapy, mainly. MicroRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. MiR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways MicroRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways
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