Proteomics analysis of colon cancer progression

Abstract

BackgroundThe aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC).MethodsA quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS).ResultsDatabase searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others.ConclusionNevertheless, the study has provided significant insights into CC stage progression for further investigation.

A Critical Review of Bottom-Up Proteomics: The Good, the Bad, and the Future of This Field

“…Mass spectrometry (MS)-based proteomics has led to the possibility of characterizing and quantifying the protein profile of biological specimens, as well as the possibility to discover their complex interactions involved in various specific pathologies. For example, various proteomic approaches combined with genomic analysis have been used in cancer research for obtaining more information about the molecular basis of tumor genesis and the development of more effective anticancer therapies [17][18][19].…”

Proteomics of Colorectal Cancer: Tumors, Organoids, and Cell Cultures—A Minireview

“…These results would support the high mutation rate observed in cancer. Saleem et al (2019) compared the proteomes of healthy tissue, non-adenomatous colon polyps, non-metastatic tumors, and metastatic tumors to identify proteins with elevated expression in the cancerous samples, such as matrix metalloproteinase-9, and decreased expression, such as caveolin-1. Similarly, Knol et al (2014) compared benign and malignant tumor proteomes by enriching the protein fractions for chromatin-binding proteins, which had shown a difference previously ( Albrethsen et al, 2010 ).…”

Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer

“…In 2018, this disease accounted for approximately 900 000 DOI: 10.1002/prca.202000056 deaths and 2 000 000 new cases worldwide. [1,2] The incidence of CRC has increased significantly in Asian countries including China, with shifting lifestyles, such as a high fat diet, smoking and alcohol abuse proposed as major contributors to CRC both in Western and Asian populations. [3,4] Environmental factors are also thought to play a major role in CRC pathogenesis but notwithstanding the underlying causes, CRC represents a major heath burden that continues to increase.…”

“…[13] On this basis, proteomic analyses have been applied to CRC in order identify diagnostic biomarkers and new therapeutic targets. [12,17,18] Previous proteomic analyses of CRC have variously defined differentially expressed proteins (DEPs) associated with the advancement of CRC, [1,2,6,12] with one study analyzing a single case of primary colon cancer and its synchronous liver metastasis. [6] Notwithstanding the findings of such studies, more work is still required to provide candidate CRC biomarkers as well as gaining better insights into its tumorigenesis.…”