Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer,

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Highlights

• •OMICS distinguish cancer cells from resistant or cancer stem cells.
• •Bactericidal antibiotics and mitochondria.
• •Linezolid and anticancer therapy.

     

Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family,

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Highlights

• •Surface loops play an essential role in SH2 domain specificity.
• •Diverse specificities may be obtained from a single SH2 domain by combinatorial mutations in the EF and BG loops.
• •The specificity of a loop mutant correlates with the sequence characteristics of the bait peptide used in its isolation.

     

Metabolic,Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

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Highlights

• •In-depth proteome profiling of primary human myeloma cells
• •Characteristics of myeloma cells are related to hypoxic bone marrow conditions
• •Myeloma cells show specific immune evasion strategies
• •Metabolic adaptations involve tumor and stroma cells

     

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma

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Highlights

• •The plasma-soluble HLA peptidome of Glioblastoma contains many tumor antigens.
• •This sHLA peptidome may serve as a rich source for disease biomarkers.
• •The sHLA peptidomes are highly correlated with the tumor's membranal HLA peptidomes.
• •The HLA peptidomes differ significantly from the proteomes of the tumors.

     

Functional Proteomics and Deep Network Interrogation Reveal a Complex Mechanism of Action of Midostaurin in Lung Cancer Cells

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Highlights

• •Anticancer activity of midostaurin but not other PKC inhibitors in NSCLC cells.
• •Mechanism of action by network-based integration of chemo- and phosphoproteomics.
• •Midostaurin polypharmacology by simultaneous inhibition of TBK1, PDPK1 and AURKA.
• •Design of synergistic drug combination with PLK1 inhibitor by pathway validation.

     

Quantitative Mass Spectrometry to Interrogate Proteomic Heterogeneity in Metastatic Lung Adenocarcinoma and Validate a Novel Somatic Mutation CDK12-G879V

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Highlights

• •Serial biopsies and autopsy from a metastatic lung cancer patient over 7 years.
• •Tumor heterogeneity characterized by quantifying the proteome and phosphoproteome.
• •Patient-specific database built using whole genome sequencing data from tumors.
• •MRM assay and functional validation of a novel lung-specific CDK12-G879V mutant.

     

Spatial Distribution of Endogenous Tissue Protease Activity in Gastric Carcinoma Mapped by MALDI Mass Spectrometry Imaging

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Highlights

• •New MALDI MS imaging sample preparation workflow reveals tissue protease activity.
• •Differential time- and inhibitor concentration-dependence confirm active proteases.
• •Mouse gastric tumor displays high protease activity compared to surrounding tissue.
• •Proteomic data and biochemical protease activity assay support MALDI MSI results.

     

DECA,A Comprehensive,Automatic Post-processing Program for HDX-MS Data*

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Highlights

• •Open source software for comprehensive HDX-MS data analysis.
• •Automatic back-exchange correction options.
• •Rigorous statistical analysis of the significance of uptake differences.
• •High quality visualization tools.

     

Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry,

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Highlights

• •LFQ-based protein patterns define glioma subgroups that correlate with genomic alterations.
• •Proteomic analysis resolves distinct pathway-level differences among glioma subtypes.
• •Distinct IDH subtype-specific tumor patterns are maintained in glioma stem cell cultures.

     

Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches

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Highlights

• •iTRAQ-based analysis of saliva samples from oral cancer patients.
• •Proteome profiling of saliva samples from patients with oral premalignant lesions.
• •Verification of salivary biomarker candidates with MRM-MS and immunoassays.
• •Identification of salivary proteins as potential biomarkers of oral cancer.

     

Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay

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Highlights

• •HPV is being introduced as the primary test in cervical cancer screening programs.
• •New biomarkers are needed for co-testing of women HPV positive in screening.
• •Analysis of plasma from women with invasive cervical cancer identified a 11-marker panel.
• •This signature shows high sensitivity and specificity to identify women with cancer.

     

gpGrouper: A Peptide Grouping Algorithm for Gene-Centric Inference and Quantitation of Bottom-Up Proteomics Data

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Highlights

• •Gene-centric inference algorithm with classification for distinguishable groups.
• •Shared peptides are split proportionally to corresponding unique peptide ratios.
• •iBAQ values are calculated for label-free, isotopic or isobaric labeling methods.
• •Universally handles single or mixed species PDX data with accurate deconvolution.

     

A Targeted Mass Spectrometry Strategy for Developing Proteomic Biomarkers: A Case Study of Epithelial Ovarian Cancer

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Highlights

• •Rigorous experimental design and data analysis for large-scale SRM studies.
• •Plasma-based biomarker signature combined with CA125 for ovarian cancer detection.
• •Broadly applicable strategy for the development of diagnostic biomarker assays.

     

Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus

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Highlights

• •C9, GSN, PON1, and PON3 validated as serum biomarker candidates of EAC.
• •Multimarker panel with AUROC of 0.93 to aid current endoscopy surveillance of BE.
• •Induction of tissue C9 in BE, dysplastic BE and EAC.
• •Alteration of complement pathway glycoproteins during BE-EAC pathogenesis.

     

Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment

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Highlights

• •Quantitative (phoshpo)proteome of primary cell cultures of patient-matched prostate CAF and NPF.
• •Key CAF-associated proteins validated using orthogonal methodologies.
• •LOXL2 inhibitors D-penicillamine and PXS-S2A impaired CAF migration and ECM alignment.
• •Pre-treatment with LOXL2 inhibitors impaired migratory capacity of RWPE-2 cells in co-culture.

     

Microvesicle Proteomic Profiling of Uterine Liquid Biopsy for Ovarian Cancer Early Detection

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Highlights

• •Microvesicle proteomics of 187 utero-tubal lavage samples for early diagnosis of HGOC.
• •Machine learning-based classification of a 9-protein signature with high predictive power.
• •Signature has 70‥ sensitivity and 76.2‥ specificity, predicting stage I lesions.

     

MaxQuant.Live Enables Global Targeting of More Than 25,000 Peptides

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Highlights

• •MaxQuant.Live controls Orbitrap mass analyzers in real-time.
• •Freely available apps enable advanced data acquisition strategies.
• •On-the-fly mass, retention time and intensity recalibration.
• •Global targeting unifies shotgun and targeted proteomics.

     

Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation*

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Highlights

• •Characterization of the phagosomal proteome comparing resting and LPS-treated BMDCs.
• •Label-free quantification determined 2843 phagosomal proteins.
• •Reduced recruitment of hydrolases and V-ATPase to phagosomes of LPS-treated cells.
• •Increased recruitment of antigen cross-presentation molecules to these phagosomes.

     

Global Proteome and Ubiquitinome Changes in the Soluble and Insoluble Fractions of Q175 Huntington Mice Brains

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Highlights

• •Quantitative changes in global proteome and ubiquitinome in Huntington's disease.
• •Differential ubiquitination of wild-type and mutant Htt in mice brain.
• •Enriched pathways include vesicle transport and mRNA processing.
• •Correlation between protein and diGly site fold changes.