Proteomic approaches for characterizing renal cell carcinoma

Abstract

Renal cell carcinoma is among the top 15 most commonly diagnosed cancers worldwide, comprising multiple subhistologies with distinct genomic, proteomic, and clinicopathological features. Proteomic methodologies enable the detection and quantitation of protein profiles associated with the disease state and have been explored to delineate the dysregulated cellular processes associated with renal cell carcinoma. In this review we highlight the reports that employed proteomic technologies to characterize tissue, blood, and urine samples obtained from renal cell carcinoma patients. We describe the proteomic approaches utilized and relate the results of studies in the larger context of renal cell carcinoma biology. Moreover, we discuss some unmet clinical needs and how emerging proteomic approaches can seek to address them. There has been significant progress to characterize the molecular features of renal cell carcinoma; however, despite the large-scale studies that have characterized the genomic and transcriptomic profiles, curative treatments are still elusive. Proteomics facilitates a direct evaluation of the functional modules that drive pathobiology, and the resulting protein profiles would have applications in diagnostics, patient stratification, and identification of novel therapeutic interventions.

Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma

“…It is also important to mention the low-throughput nature of this technique, which made it less favorable for use as a tool for protein profiling ( 104 ). Techniques like flow cytometry or immunohistochemistry have also been used to detect the expression of dysregulated proteins, but over the past two decades, mass spectrometry (MS) has been employed to assess the proteome in RCC ( 105 ). The glycolytic enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) and small nuclear ribonucleoprotein polypeptide F (SNRPF) were shown to be significantly dysregulated in ccRCC by liquid chromatography-tandem mass spectrometry (LC-MS/MS).…”

Renal oncocytoma: a challenging diagnosis

“…Proteomic expression profiling has highlighted the accumulation of mitochondrial proteins in renal oncocytoma. Some of these proteins correspond to traditional IHC markers used to distinguish renal oncocytoma from ChRCC [81,82].…”

Diagnostic and Prognostic Biomarkers in Renal Clear Cell Carcinoma

“…Next-generation sequencing (NGS) and other high-throughput analyses provide a wealth of information regarding the abundance of genomic and transcriptomic alterations but often fail to fully characterize the biological state of the tumor as protein modifications are missed at these levels of analysis [61]. Post-translational modifications (PTMs) are enzyme-catalyzed additions of specific functional groups to proteins that promote a variety of biological functions [62].…”

“…Proteomic analyses have also been influential in the categorizing of ccRCC, as molecular subgrouping is a useful tool in stratifying patients for precision therapeutics, such as for the use of VEGF inhibitors versus immune-based therapies [32,65]. Despite a multitude of studies over the past 15 years that have uncovered a generalized proteomic profile for ccRCC, none have achieved an adequately comprehensive characterization depicting the necessary linkage between genomic and transcriptomic aberrations, phenotypic presentation, and independent validation to promote clinical utility [61]. Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) was the most commonly utilized technique to analyze peptide fractions for diagnostic studies, with validation by western-and 6immune-blotting (serum/plasma and urine) and immunohistochemistry (IHC) (tissue) (Table 4).…”