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. 2019 Dec 28;16:44.
doi: 10.1186/s12014-019-9264-y. eCollection 2019.

Proteomics Analysis of Colon Cancer Progression

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Free PMC article

Proteomics Analysis of Colon Cancer Progression

Saira Saleem et al. Clin Proteomics. .
Free PMC article

Abstract

Background: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC).

Methods: A 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).

Results: Database 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.

Conclusion: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

Keywords: Biomarkers; Colon cancer; Orbitrap fusion; iTRAQ proteomics.

Conflict of interest statement

Competing interestsThe authors declared that they have no competing interests.

Figures

Fig. 1
Fig. 1
Selected clusters of functional significance 1: non-adenomatous colon polyp/non cancer 2: colon cancer (non-metastatic)/non cancer 3: colon cancer (metastatic)/non cancer Responses are defined as I: increased (ratio > ± 1 standard deviation (SD) of log2 median), D: decreased ratio (< ± 1 std dev of log2 median), U: unchanged (ratio = ± 1 standard deviation (SD) of log2 median). The colored lines represent proteins. Accession numbers for first 11 proteins in each cluster are shown in the legend
Fig. 2
Fig. 2
a STRING analysis of proteins increased in non-metastatic and metastatic stages of colon cancer (UII). b STRING analysis of proteins decreased in non-metastatic and metastatic stages of colon cancer (UDD). Proteins are shown as nodes and the color of each link defined the type of evidence available for the interaction between two proteins (e.g. blue: co-occurrence, black: co-expression, purple: experimental, aqua: databases, green: text mining and light blue is homology.)
Fig. 2
Fig. 2
a STRING analysis of proteins increased in non-metastatic and metastatic stages of colon cancer (UII). b STRING analysis of proteins decreased in non-metastatic and metastatic stages of colon cancer (UDD). Proteins are shown as nodes and the color of each link defined the type of evidence available for the interaction between two proteins (e.g. blue: co-occurrence, black: co-expression, purple: experimental, aqua: databases, green: text mining and light blue is homology.)
Fig. 3
Fig. 3
a Western blot expression of CAV-1 (21–24 kDa) and MMP-9 (65–92 kDa) identified in diseased and non-cancer colon tissues NC: non-cancer normal colon lining, NAP non-adenomatous colon polyp, CC NM colon cancer (non-metastatic), CC M colon cancer (metastatic), I–III TNM staging according to AJCC 8th Edition guidelines. b Box and whisker plot of the CAV-1 expression by western blotting versus normal colon or disease stage

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