The following are available online at https://www.mdpi.com/article/10.3390/cancers14020449/s1. Supplementary Figures. Figure S1: Distribution of pathological CSF samples (without healthy ones) among each phase of study and the different groups according to the incidence of the pathology, depending on the infiltration (CSF +/− LM) and the primary tumor (hematologic and solid tumor). Figure S2: Quality control images of the planar protein microarrays generated. Figure S3: A quantile normalization in planar protein microarrays. Figure S4: Coomasie gels which indicate protein distribution across samples. Figure S5: Venn diagrams of total identified proteins with LC-MS/MS. Figure S6: Plots showing the functional proteins using the Reactome for different conditions. Figure S7: Differential protein profiles within CSF + LM according to primary tumor (Lymphoma) by protein microarrays. Figure S8: Differential protein profiles within CSF + LM according to primary tumor (Leukemia) by protein microarrays. Figure S9: Differential protein profiles within CSF + LM according to primary tumor (Lymphoma) by affinity proteomics. Figure S10: Differential protein profiles within CSF + LM according to primary tumor (Leukemia) by affinity proteomics. Figure S11: Summary of the multipronged proteomics characterization among the different phases of study. Supplementary Tables. Table S1: Table of clinical-biological characteristics from the whole CSF samples used in the study. Table S2: Antibodies list used in Planar Protein Microarrays. Table S3: Antibodies list used in Beads Suspension Microarrays. Table S4: Protein identification with LC-MS/MS among the different strategies and their emPAI quantification. Table S5: Boxplots of the protein identified in validation and confirmation phases, respectively, comparing the different groups of study. Table S6: Intensity data results from Planar Protein Microarrays. Table S7: Intensity data results from Beads Suspension Microarrays. Table S8: ROC analysis list of potential biomarker panel on CSF +/− LM and the different comparisons by protein arrays and affinity proteomics.

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