![]() Emerging molecular biomarkers – blood-based strategies to detect and monitor cancer. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Predictive validity of animal pain models? A comparison of the pharmacokinetic–pharmacodynamic relationship for pain drugs in rats and humans. ![]() 3 Whiteside GT, Adedoyin A, Leventhal L.Assessment of tumor characteristic gene expression in cell lines using a tissue similarity index (TSI). Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest References Finally, this perspective presents the background, rationale and strategy for using tissue-directed high-resolution/accuracy MS-based shotgun proteomics to detect genuine tumor proteins in the peripheral blood of a patient diagnosed with nonmetastatic cancer, employing concurrent liquid chromatography–MS analysis of immunodepleted clinical tissue and blood specimens. Herein, we show that the removal of abundant blood-derived proteins from solid tissue specimens is of equal importance to depletion of body fluids and recommend its routine use in the context of biological discovery and/or cancer biomarker research. We also applied immunodepletion of abundant blood-derived proteins to various tissue types (e.g., adipose tissue and breast tissue) showing unambiguously that the removal of abundant blood-derived proteins represents a powerful tool for the reproducible profiling of tissue proteomes. This includes the activation of the lipogenic pathway characterized by increased expression of adipophilin (PLIN2) along with ‘cadherin switching’, a phenomenon indicative of transcriptional reprogramming linked to renal epithelial dedifferentiation. Integrative analysis of data from this approach and genomic data obtained from the same type of tumor revealed concordant key pathways and protein targets germane to clear cell renal cell carcinoma. Thus, we optimized and applied simultaneous immunodepletion of blood-derived proteins from solid tissue and peripheral blood, using clear cell renal cell carcinoma as a model disease. Hence, the dynamic range impediment to biomarker discovery remains a formidable obstacle, regardless of clinical sample type (solid tissue and/or body fluid). Often overlooked, clinical tissue specimens also contain a formidable amount of highly abundant blood-derived proteins present in tissue-embedded networks of blood/lymph capillaries and interstitial fluid. Immunodepletion of clinical body fluid specimens (e.g., serum/plasma) for the removal of highly abundant proteins is a reasonable and reproducible solution. The discovery of clinically relevant cancer biomarkers using mass spectrometry (MS)-based proteomics has proven difficult, primarily because of the enormous dynamic range of blood-derived protein concentrations and the fact that the 22 most abundant blood-derived proteins constitute approximately 99% of the total plasma protein mass.
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