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Supplementary Tables 1 - 10 from microRNA Expression Profiles Identify Subtypes of Mantle Cell Lymphoma with Different Clinicobiological Characteristics

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posted on 2023-03-31, 17:04 authored by Alba Navarro, Guillem Clot, Miriam Prieto, Cristina Royo, Maria Carmela Vegliante, Virginia Amador, Elena Hartmann, Itziar Salaverria, Sílvia Beà, Jose Ignacio Martín-Subero, Andreas Rosenwald, German Ott, Adrian Wiestner, Wyndham H. Wilson, Elías Campo, Luis Hernández

PDF file - 364K, Supplementary Table 1. Comparison of main features of MCL patients from the different studied series; Supplementary Table 2. Normalized expression in miRs with SD variation higher than 50th percentile and detectable expression >25% of cases; Supplementary Table 3a. Subgroups of leukemic MCL according IGHV status and core miR expression clusters and related data; Supplementary Table 3b. Additional data in leukemic MCL with studied mRNA by arrays; Supplementary Table 4a. Results of supervised Limma analysis between Unmutated vs Mutated IGHV MCL; Supplementary Table 4b. Results of supervised Limma analysis between High vs Low SOX11 expressing MCL; Supplementary Table 5a. Overlapping of miR lists from Venn diagram (Supplementary Figure 2); Supplementary Table 5b. Results of supervised Limma analysis between the different MCL subgroups; Supplementary Table 6a. miR expression fold changes for IGHV mutational status in the 16 MCL series compared to the whole sample set; Supplementary Table 6b. Expression fold changes between IGHV mutational status categories in the 16 MCL series for those genes predicted to be targets for IGHV-related miRs and involved in significant enriched pathways; Supplementary Table 7a. MAGIA output for inverse Spearman correlation between IGHV-related miRs and mRNA expression values in 16 leukemic MCL; Supplementary Table 7b. Significant results from GSEA analysis from pre-ranked list of correlations between IGHV-related miRs and their putative targets; Supplementary Table 7c. Gene lists from significant GSEA analysis results from pre-ranked list of correlations between IGHV-related miRs and their putative targets; Supplementary Table 8a. MAGIA output for inverse Spearman correlation between miR-708 and miR-455-5p/3p and mRNA expression values in 16 leukemic MCL; Supplementary Table 8b. Enrichment analysis (g:Profiler) significant results from inversely correlated predicted targets for miR-708 and miR-455-5p/3p (top 75% subset); Supplementary Table 9. Proliferation signature calculations in the 16 leukemic MCL with gene expression data; Supplementary Table 10. Correlation analysis of miR expression and MCL proliferation signature.

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ARTICLE ABSTRACT

Purpose: microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL).Experimental Design: Expression profiling of 664 miRNAs was investigated using a high-throughput quantitative real-time PCR platform in 30 leukemic MCLs. Statistical and bioinformatic analyses were conducted to define miRNAs associated with different clinicopathologic parameters. Gene expression profiling was investigated by microarrays in 16 matching cases to study the potential genes and pathways targeted by selected miRNAs. The prognostic value of miR-34a was investigated in 2 independent series of 29 leukemic and 50 nodal MCLs.Results: Robust consensus clustering defined 2 main MCL subgroups with significant differences in the immunoglobulin (IGHV) mutational status, SOX11 expression, genomic complexity, and nodal clinical presentation. Supervised analyses of IGHV and SOX11 categories identified 17 and 22 miRNAs differentially expressed, respectively. Enriched targets of these miRNAs corresponded to relevant pathways in MCL pathogenesis such as DNA stress response, CD40 signaling, and chromatin modification. In addition, we found 7 miRNAs showing prognostic significance independently of IGHV status and SOX11 expression. Among them, miR-34a was also associated with poor prognosis in 2 independent series of leukemic and nodal MCL, and in cooperation with high expression of the MYC oncogene.Conclusion: We have identified miRNAs and target pathways related to clinical and biologic variants of leukemic MCL, and validated miR-34a as a prognostic marker in MCL. Clin Cancer Res; 19(12); 3121–9. ©2013 AACR.