References of "Sajic, Tatjana"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailA new class of protein biomarkers based on subcellular distribution: application to a mouse liver cancer model.
Sajic, Tatjana; Ciuffa, Rodolfo; Lemos, Vera et al

in Scientific reports (2019), 9(1), 6913

To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in ... [more ▼]

To-date, most proteomic studies aimed at discovering tissue-based cancer biomarkers have compared the quantity of selected proteins between case and control groups. However, proteins generally function in association with other proteins to form modules localized in particular subcellular compartments in specialized cell types and tissues. Sub-cellular mislocalization of proteins has in fact been detected as a key feature in a variety of cancer cells. Here, we describe a strategy for tissue-biomarker detection based on a mitochondrial fold enrichment (mtFE) score, which is sensitive to protein abundance changes as well as changes in subcellular distribution between mitochondria and cytosol. The mtFE score integrates protein abundance data from total cellular lysates and mitochondria-enriched fractions, and provides novel information for the classification of cancer samples that is not necessarily apparent from conventional abundance measurements alone. We apply this new strategy to a panel of wild-type and mutant mice with a liver-specific gene deletion of Liver receptor homolog 1 (Lrh-1(hep-/-)), with both lines containing control individuals as well as individuals with liver cancer induced by diethylnitrosamine (DEN). Lrh-1 gene deletion attenuates cancer cell metabolism in hepatocytes through mitochondrial glutamine processing. We show that proteome changes based on mtFE scores outperform protein abundance measurements in discriminating DEN-induced liver cancer from healthy liver tissue, and are uniquely robust against genetic perturbation. We validate the capacity of selected proteins with informative mtFE scores to indicate hepatic malignant changes in two independent mouse models of hepatocellular carcinoma (HCC), thus demonstrating the robustness of this new approach to biomarker research. Overall, the method provides a novel, sensitive approach to cancer biomarker discovery that considers contextual information of tested proteins. [less ▲]

Detailed reference viewed: 16 (0 UL)
Full Text
Peer Reviewed
See detailSimilarities and Differences of Blood N-Glycoproteins in Five Solid Carcinomas at Localized Clinical Stage Analyzed by SWATH-MS.
Sajic, Tatjana; Liu, Yansheng; Arvaniti, Eirini et al

in Cell reports (2018), 23(9), 2819-28315

Cancer is mostly incurable when diagnosed at a metastatic stage, making its early detection via blood proteins of immense clinical interest. Proteomic changes in tumor tissue may lead to changes ... [more ▼]

Cancer is mostly incurable when diagnosed at a metastatic stage, making its early detection via blood proteins of immense clinical interest. Proteomic changes in tumor tissue may lead to changes detectable in the protein composition of circulating blood plasma. Using a proteomic workflow combining N-glycosite enrichment and SWATH mass spectrometry, we generate a data resource of 284 blood samples derived from patients with different types of localized-stage carcinomas and from matched controls. We observe whether the changes in the patient's plasma are specific to a particular carcinoma or represent a generic signature of proteins modified uniformly in a common, systemic response to many cancers. A quantitative comparison of the resulting N-glycosite profiles discovers that proteins related to blood platelets are common to several cancers (e.g., THBS1), whereas others are highly cancer-type specific. Available proteomics data, including a SWATH library to study N-glycoproteins, will facilitate follow-up biomarker research into early cancer detection. [less ▲]

Detailed reference viewed: 17 (0 UL)
Full Text
Peer Reviewed
See detailSystematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells.
Liu, Yansheng; Borel, Christelle; Li, Li et al

in Nature communications (2017), 8(1), 1212

Down syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and protein turnover in fibroblasts from ... [more ▼]

Down syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and matched controls. The integration of the steady-state and turnover proteomic data indicates that protein-specific degradation of members of stoichiometric complexes is a major determinant of T21 gene dosage outcome, both within and between individuals. This effect is not apparent from genomic and transcriptomic data. The data also reveal that T21 results in extensive proteome remodeling, affecting proteins encoded by all chromosomes. Finally, we find broad, organelle-specific post-transcriptional effects such as significant downregulation of the mitochondrial proteome contributing to T21 hallmarks. Overall, we provide a valuable proteomic resource to understand the origin of DS phenotypic manifestations. [less ▲]

Detailed reference viewed: 21 (0 UL)