Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development
<b>Background:</b> 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...
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MDPI AG
2020-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/619 |
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| author | Arthur T. Kopylov Alexander A. Stepanov Kristina A. Malsagova Deepesh Soni Nikolay E. Kushlinsky Dmitry V. Enikeev Natalia V. Potoldykova Andrey V. Lisitsa Anna L. Kaysheva |
| author_facet | Arthur T. Kopylov Alexander A. Stepanov Kristina A. Malsagova Deepesh Soni Nikolay E. Kushlinsky Dmitry V. Enikeev Natalia V. Potoldykova Andrey V. Lisitsa Anna L. Kaysheva |
| author_sort | Arthur T. Kopylov |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Results:</b> 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 (<i>p</i> < 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. <b>Conclusions:</b> 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. |
| first_indexed | 2024-12-23T06:53:42Z |
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| language | English |
| last_indexed | 2024-12-23T06:53:42Z |
| publishDate | 2020-01-01 |
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| series | Molecules |
| spelling | doaj.art-7a3365a93592433fad0ad53d87bb728f2022-12-21T17:56:22ZengMDPI AGMolecules1420-30492020-01-0125361910.3390/molecules25030619molecules25030619Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of DevelopmentArthur T. Kopylov0Alexander A. Stepanov1Kristina A. Malsagova2Deepesh Soni3Nikolay E. Kushlinsky4Dmitry V. Enikeev5Natalia V. Potoldykova6Andrey V. Lisitsa7Anna L. Kaysheva8V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, RussiaV.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, RussiaV.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, RussiaV.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, RussiaN.N. Blokhin Russian Cancer Research Center, 115478 Moscow, RussiaInstitute of Urology and Reproductive Health (Sechenov University), 119992 Moscow, RussiaInstitute of Urology and Reproductive Health (Sechenov University), 119992 Moscow, RussiaEast China University of Technology, Nanchang 330013, ChinaV.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia<b>Background:</b> 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. <b>Results:</b> 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 (<i>p</i> < 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. <b>Conclusions:</b> 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.https://www.mdpi.com/1420-3049/25/3/619colorectal cancerprotein patterndigital medicineultra-high resolution mass spectrometrypost-translational modificationsomicspostgenomic data |
| spellingShingle | Arthur T. Kopylov Alexander A. Stepanov Kristina A. Malsagova Deepesh Soni Nikolay E. Kushlinsky Dmitry V. Enikeev Natalia V. Potoldykova Andrey V. Lisitsa Anna L. Kaysheva Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development Molecules colorectal cancer protein pattern digital medicine ultra-high resolution mass spectrometry post-translational modifications omics postgenomic data |
| title | Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development |
| title_full | Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development |
| title_fullStr | Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development |
| title_full_unstemmed | Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development |
| title_short | Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development |
| title_sort | revelation of proteomic indicators for colorectal cancer in initial stages of development |
| topic | colorectal cancer protein pattern digital medicine ultra-high resolution mass spectrometry post-translational modifications omics postgenomic data |
| url | https://www.mdpi.com/1420-3049/25/3/619 |
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