Alterations of the Plasma Peptidome Profiling in Colorectal Cancer Progression

Abstract

Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the pathological alterations within an organ and tissues might be reflected in serum or plasma proteomic/peptidic patterns. The aim of the study was to follow the changes in the plasma peptides associated to colorectal cancer progression by mass spectrometry. This study included 27 adenoma, 67 CRC (n = 33 I-II stage and n = 34 III-IV stage), 23 liver metastasis from CRC patients and 34 subjects disease-free as controls. For plasma peptides analysis, samples purification was performed on the Nanoporous Silica Chips technology followed by matrix-assisted laser desorption/ionisation-time of flight analysis. Since the high complexity of the obtained dataset, multivariate statistical analysis, and discriminant pattern recognition were performed for study groups classification. Forty-four of 88 ionic species were successfully identified as fragments of peptides and proteins physiologically circulating in the blood and belonging to immune and coagulation systems and inflammatory mediators. Many peptides clustered into sets of overlapping sequences with ladder-like truncation clearly associated to proteolytic processes of both endo- and exoproteases activity. Comparing to controls, a different median ion intensity of the group-type fragments distribution was observed. Moreover, the degradation pattern obtained by proteolytic cleavage was different into study groups. This pattern was specific and characteristic of each group: controls, colon tumour disease (including adenoma and CRC), and liver metastasis, revealing a role as biomarker in early diagnosis and prognosis. Our findings highlighted peculiar changes in protease activity characteristic of CRC progression from pre-cancer lesion to metastatic disease. J. Cell. Physiol. 231: 915-925, 2016. © 2015 Wiley Periodicals, Inc.

Clinical applications of plasma proteomics and peptidomics: Towards precision medicine

“…Since plasma is a valuable source of cancer biomarkers, analysis of proteins and peptides in plasma has gained momentum in cancer clinical research and is experiencing significant uptake in a variety of applications [13, 135, 183]. Plasma proteomics and peptidomics have been successfully applied to various cancer studies, such as ovarian cancer, breast cancer, gastric cancer, melanoma, colorectal cancer, prostate cancer, bladder cancer, lung cancer, and esophageal cancer [134, 258–270]. To establish protein fingerprints for cancer diagnosis and grade assessment, differential proteins and peptides in plasma are compared between healthy controls and cancer groups, or at different stages of the cancer progression.…”

The characterization of cell surface receptor complexes by affinity chromatography, liquid chromatography and tandem mass spectrometry

“…Evidence was provided that Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) and Growth Differentiation Factor 15 (GDF15) may serve as biomarkers of colon cancer (Lancrajan et al, 2015). Differential activity of endo and exopeptidase, including changes in Bradykinin, was reflected over the progression of colorectal cancer in plasma samples (Bedin et al, 2015). Protein assays of circulating proteins such a leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid-binding protein 4, and tissue plasminogen activator [t-PA]) cathepsin D might be used to detect insulin resistance (IR), the precursor of type 2 diabetes (Nowak et al, 2016).…”

Contribution of the plasma and lymph Degradome and Peptidome to the MHC Ligandome

“…A statistically significant diverse peptidome could be mapped between the two groups 46 . Similar analyses have mapped degradome/peptidomes in patients with oral, breast, ovarian, colon-rectal cancer as well as metastasis from different malignancies [24][25][26]28,31,32,36,37,40,43,[101][102][103] . All these analyses point to the importance of the peptidome/degradome, present in biological fluid, as an important tool for biomarker discovery 37 .…”

“…Indeed a degradome for the alternative pathway has been mapped in lymph and plasma collected from healthy individuals [1][2][3]87,119,129,130 . On the other hand the activity of the complement cascade is highly increased in acute and chronic inflammatory conditions as well as degenerative pathologies in every parenchymal organ [24][25][26]31,32,36,37,101,121 .…”