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Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients.

ABSTRACT: Age at diagnosis, stage, and MYCN amplification are the cornerstones of the risk-stratification score of neuroblastoma that enables defining patients at low- and high risk. Refinement of this stratification is needed to optimize standard treatment and to plan future clinical trials. We investigated whether two parental imprinted miRNAs (miR-487b and miR-516a-5p) may lead to a risk score with a better discrimination. Expression levels of maternal miR-487b and paternal miR-516a-5p were determined using quantitative RT-PCR both for 231 neuroblastoma tumors (derivation set) and 101 independent neuroblastoma tumors (validation set). Survival outcomes were overall survival (OS) and disease-free survival (DFS). Multivariable Cox models were developed from derivation set and their performance evaluated using Akaike's information criterion (AIC) (goodness-of-fit) and time-dependent area under curves (discrimination). The selected model was validated using internal and external validation. The prognostic model including current prognostic factors plus miR-487b, miR-516a-5p, and interaction between two miRNAs was selected. Performance of this model was better in terms of both predictive ability (smallest AIC) and discrimination power (AUC close to 0.70). This model identifies three risk groups: high (3), intermediate (2), and low (1). Hazard ratios (HR) across risk groups were HR2/1 = 6.3 (2.7-14.6), HR3/1 = 14.8 (7.2-30.2) for OS and HR2/1 = 2.8 (1.5-5.4), HR3/1 = 7.2 (3.9-13.4) for DFS. The rank between these three risk groups was maintained and validated when performing internal and external validation. Expression of maternal miR-487b and paternal miR-516a-5p improves the risk stratification. This better discrimination at diagnosis is of clinical utility both for current and future treatments of neuroblastoma patients.

SUBMITTER: Gattolliat CH

PROVIDER: S-EPMC4303168 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients.

Gattolliat Charles-Henry CH Le Teuff Gwénaël G Combaret Valérie V Mussard Eugénie E Valteau-Couanet Dominique D Busson Pierre P Bénard Jean J Douc-Rasy Sétha S

Cancer medicine 20140613 4

Age at diagnosis, stage, and MYCN amplification are the cornerstones of the risk-stratification score of neuroblastoma that enables defining patients at low- and high risk. Refinement of this stratification is needed to optimize standard treatment and to plan future clinical trials. We investigated whether two parental imprinted miRNAs (miR-487b and miR-516a-5p) may lead to a risk score with a better discrimination. Expression levels of maternal miR-487b and paternal miR-516a-5p were determined ...[more]

PMID: 24931722

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Project description:ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC.Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models.Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063).Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.

Dataset Information

Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients.

Publications

Expression of two parental imprinted miRNAs improves the risk stratification of neuroblastoma patients.

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