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Polymorphisms in microRNA-related genes are associated with survival of patients with T-cell lymphoma.

ABSTRACT: OBJECTIVE: Elaborate evaluation of prognosis of T-cell lymphoma (TCL) is vital for current therapy and future stratified and individualized therapy. MicroRNAs (miRNAs) play important roles in cancer development and prognosis. We aimed to assess the effects of single nucleotide polymorphisms (SNPs) in miRNA-related genes on the survival of patients with TCL. PATIENTS AND METHODS: We genotyped 13 SNPs selected from 12 miRNA-related genes in 220 TCL patients and explored the association of SNPs with survival. RESULTS: Among the 13 SNPs, four (DROSHA rs6877842, DICER rs3742330, mir149 rs2292832, and mir499 rs3746444) were significantly associated with TCL survival after adjusting for subtype and International Prognostic Index score. In stratified analyses, all four SNPs remained significantly associated with survival in patients with mature T type. Of the four SNPs, only mir149 rs2292832 was not significantly associated with survival in patients with an International Prognostic Index score of 0-1. Furthermore, a dose-dependent cumulative effect of the four SNPs on TCL survival was observed by counting the number of unfavorable genotypes. Survival tree analysis also showed higher order interactions between these SNPs. CONCLUSION: The results suggested that miRNA-related polymorphisms are associated with survival of TCL patients; thus, they may be used individually and jointly to predict survival of patients with TCL.

SUBMITTER: Li X

PROVIDER: S-EPMC3958464 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Polymorphisms in microRNA-related genes are associated with survival of patients with T-cell lymphoma.

Li Xi X Tian Xiaobo X Zhang Bo B Chen Jieping J

The oncologist 20140221 3

<h4>Objective</h4>Elaborate evaluation of prognosis of T-cell lymphoma (TCL) is vital for current therapy and future stratified and individualized therapy. MicroRNAs (miRNAs) play important roles in cancer development and prognosis. We aimed to assess the effects of single nucleotide polymorphisms (SNPs) in miRNA-related genes on the survival of patients with TCL.<h4>Patients and methods</h4>We genotyped 13 SNPs selected from 12 miRNA-related genes in 220 TCL patients and explored the associatio ...[more]

PMID: 24563077

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Project description:BackgroundThough immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear.MethodsWe investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA.ResultsBy comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes.ConclusionsWe used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

Dataset Information

Polymorphisms in microRNA-related genes are associated with survival of patients with T-cell lymphoma.

Publications

Polymorphisms in microRNA-related genes are associated with survival of patients with T-cell lymphoma.

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