Apolipoprotein E Overexpression Is Associated With Tumor Progression and Poor Survival in Colorectal Cancer

Zhao, Zhixun; Zou, Shuangmei; Guan, Xu; Wang, Meng; Jiang, Zheng; Liu, Zheng; Li, Chunxiang; Lin, Huixin; Liu, Xiuyun; Yang, Rulai; Gao, Yibo; Wang, Xishan

doi:10.3389/fgene.2018.00650

Cited by 58 publications

(40 citation statements)

References 23 publications

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“…Apolipoprotein E is involved in DNA synthesis, cell proliferation, angiogenesis, and metastasis, and changes of these functions might induce tumorigenesis or progression [19].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

et al. 2020

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Background and Aims: Extrahepatic cholangiocarcinoma (CCA) without liver-fluke is increasing. Multifactorial carcinogenesis makes it hard to find biomarkers related to CCA. Although there are a few studies of bile proteomics, these showed different protein profiles because of having heterogeneous groups of patients and different sampling methods. Our aim was to identify the specific bile proteins of extrahepatic CCA patients. Methods: We collected bile from 23 patients undergoing endoscopic nasobiliary drainage in Korea University Guro Hospital from May 2018 to January 2019. The CCA group included 18 patients diagnosed with extrahepatic CCA, and the control group included 5 patients with benign biliary conditions. We analyzed bile proteome using liquid chromatography mass spectrometry. We compared the relative abundance of various proteins in the CCA and control groups. Results: In all, we identified a total of 245 proteins in the bile of CCA and control patients. Increased top 14 proteins in CCA patients were immunoglobulin kappa light chain, apolipoprotein B, inter-alpha-trypsin inhibitor heavy chain H4, apolipoprotein E, Mucin 5B, inter-alpha-trypsin inhibitor heavy chain H1, apolipoprotein A-IV, intercellular adhesion molecule 1, complement C7, complement C5, apolipoprotein C-III, albumin, antithrombin-III, and apolipoprotein A-II. However, the significantly increased proteins in bile of CCA patients comparing with control patients were immunoglobulin kappa light chain, apolipoprotein E, albumin, apolipoprotein A-I, antithrombin-III, α1-antitrypsin, serotransferrin, immunoglobulin heavy constant mu, immunoglobulin J chain, complement C4-A, and complement C3 (p<0.05). Conclusions: In this study, we identified several proteins that were significantly increased in the bile of extrahepatic CCA. Further study is needed to validate them as potential tumor-associated proteins that may be potential biomarkers for CCA.

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“…Apolipoprotein E is involved in DNA synthesis, cell proliferation, angiogenesis, and metastasis, and changes of these functions might induce tumorigenesis or progression [19].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

et al. 2020

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“…Apolipoproteins are a large family of proteins mainly involved in lipid particle remodeling, lipid transport, binding, and clearance. Changing their levels covers a wide variety of pathologies [63]. Some of them, like apolipoproteins APOE, APOC1, and APOA1, are associated with aggressive behavior of tumor growth [64].…”

Section: The Prognostic Significance Of Lipid Metabolismmentioning

confidence: 99%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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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.

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“…52) was present in the IL-1, IL-33, and EGFR pathways ( Supplementary Figures 5 and 6). As an added factor for consideration, irregularities in the expression levels of these upstream and downstream genes have been implicated in tumorigenesis [54][55][56][57][58].…”

Section: Inflammation Pathwaysmentioning

confidence: 99%

Down syndrome iPSC model: endothelial perspective on tumor development

et al. 2020

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Trisomy 21 (T21), known as Down syndrome (DS), is a widely studied chromosomal abnormality. Previous studies have shown that DS individuals have a unique cancer profile. While exhibiting low solid tumor prevalence, DS patients are at risk for hematologic cancers, such as acute megakaryocytic leukemia and acute lymphoblastic leukemia. We speculated that endothelial cells are active players in this clinical background. To this end, we hypothesized that impaired DS endothelial development and functionality, impacted by genome-wide T21 alterations, potentially results in a suboptimal endothelial microenvironment with the capability to prevent solid tumor growth. To test this hypothesis, we assessed molecular and phenotypic differences of endothelial cells differentiated from Down syndrome and euploid iPS cells. Microarray, RNA-Seq, and bioinformatic analyses revealed that most significantly expressed genes belong to angiogenic, cytoskeletal rearrangement, extracellular matrix remodeling, and inflammatory pathways. Interestingly, the majority of these genes are not located on Chromosome 21. To substantiate these findings, we carried out functional assays. The obtained phenotypic results correlated with the molecular data and showed that Down syndrome endothelial cells exhibit decreased proliferation, reduced migration, and a weak TNF-α inflammatory response. Based on this data, we provide a set of genes potentially associated with Down syndrome's elevated leukemic incidence and its unfavorable solid tumor microenvironment-highlighting the potential use of these genes as therapeutic targets in translational cancer research.

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Apolipoprotein E Overexpression Is Associated With Tumor Progression and Poor Survival in Colorectal Cancer

Cited by 58 publications

References 23 publications

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Down syndrome iPSC model: endothelial perspective on tumor development

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