Background:
Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent
tumors, which are typically asymptotic. Searching for reliable
biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative
proteome-scaled analysis. The main goal of the study was to establish a constellation of
protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166
proteins for patients in stages I-II and III-IV, correspondingly. Plenty of
proteins (44
proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I-II of CRC. Among them, some
cytokines (
Clusterin (CLU),
C4b-binding protein (C4BP), and CD59
glycoprotein (CD59), etc.) were the most prominent and the
lectin pathway was specifically enhanced in patients with CRC. Significant alterations in
Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in
tumor growth and the
malignancy process. Other markers (
Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-
glycoprotein (A1BG),
Haptoglobin (HP), and
Leucine-rich alpha-2-
glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in
cancer development but also to exactly promote
tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of
colorectal cancer, including
kininogen 1
protein (T327-p),
alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e.,
vitamin D-binding protein (K75-ac and K370-ac) and
plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of
cytokines and
proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since
tumor growth is tightly associated with chronic aseptic
inflammation and concatenated
malignancy related to loss of extracellular matrix stability. Due attention should be paid to
Apolipoprotein E (
APOE),
Apolipoprotein C1 (APOC1), and
Apolipoprotein B-100 (
APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native
proteins was not detected confidently.