Leucine-rich alpha-2-glycoprotein-1 is up-regulated in colorectal cancer and is a tumor promoter

Zhang, Qian; Huang, Rui; Tang, Qingchao; Yu, Yang; Huang, Quanlong; Chen, Yinggang; Wang, Guiyu; Wang, Xishan

doi:10.2147/ott.s153375

Cited by 33 publications

(37 citation statements)

References 27 publications

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“…Since tumor progression is tightly associated with re-arrangement of the extracellular matrix, employment of AMBP, ITIH1, and ITIH4 may also support the net benefit for early detection of CRC and designation of probable cell migration. However, results of ITIH2 measurement contradict the previously reported data [47,48], which makes early recognition of CRC less confident and specific (Supplementary Materials Table S5).…”

Section: Discussioncontrasting

confidence: 67%

“…Nevertheless, another family member, ITIH2, is typically exhausted or displays significant down-regulation in CRC pathology (up to 61% of tumor cases, [47]), which is at odds with the obtained results in our study on positive regulation of ITIH2 (FC = 2.18, Supplementary Materials Table S4). Previously, a strong link between the expression levels of ITIH2 and estrogen levels has been demonstrated, since ITIH2 contains an estrogen-binding domain which might be critical for metastasis and tumor growth because estrogen has a profound effect on extracellular matrix integrity [48]. However, due to the fact that our results do not completely agree with earlier established reports, we are reluctant to make a final conclusion in relation to ITIH2 levels in CRC patients.…”

Section: Relationship Between Inter-α-trypsin Inhibitor Heavy Chains contrasting

confidence: 73%

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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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Section: Discussioncontrasting

confidence: 67%

Section: Relationship Between Inter-α-trypsin Inhibitor Heavy Chains contrasting

confidence: 73%

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

et al. 2020

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“…In addition, the protein is secreted and may therefore end up in blood or stool. Indeed, increased protein levels of LRG1 in plasma have been reported for colorectal cancer and colon adenoma patients [40,43,44]. Altogether, for the majority of these biomarker proteins their potential involvement in tumor biology has been demonstrated.…”

Section: Discussionmentioning

confidence: 98%

Proteins in stool as biomarkers for non‐invasive detection of colorectal adenomas with high risk of progression

Komor

Bosch

Coupé

et al. 2020

The Journal of Pathology

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Screening to detect colorectal cancer (CRC) in an early or premalignant state is an effective method to reduce CRC mortality rates. Current stool‐based screening tests, e.g. fecal immunochemical test (FIT), have a suboptimal sensitivity for colorectal adenomas and difficulty distinguishing adenomas at high risk of progressing to cancer from those at lower risk. We aimed to identify stool protein biomarker panels that can be used for the early detection of high‐risk adenomas and CRC. Proteomics data (LC–MS/MS) were collected on stool samples from adenoma (n = 71) and CRC patients (n = 81) as well as controls (n = 129). Colorectal adenoma tissue samples were characterized by low‐coverage whole‐genome sequencing to determine their risk of progression based on specific DNA copy number changes. Proteomics data were used for logistic regression modeling to establish protein biomarker panels. In total, 15 of the adenomas (15.8%) were defined as high risk of progressing to cancer. A protein panel, consisting of haptoglobin (Hp), LAMP1, SYNE2, and ANXA6, was identified for the detection of high‐risk adenomas (sensitivity of 53% at specificity of 95%). Two panels, one consisting of Hp and LRG1 and one of Hp, LRG1, RBP4, and FN1, were identified for high‐risk adenomas and CRCs detection (sensitivity of 66% and 62%, respectively, at specificity of 95%). Validation of Hp as a biomarker for high‐risk adenomas and CRCs was performed using an antibody‐based assay in FIT samples from a subset of individuals from the discovery series (n = 158) and an independent validation series (n = 795). Hp protein was significantly more abundant in high‐risk adenoma FIT samples compared to controls in the discovery (p = 0.036) and the validation series (p = 9e‐5). We conclude that Hp, LAMP1, SYNE2, LRG1, RBP4, FN1, and ANXA6 may be of value as stool biomarkers for early detection of high‐risk adenomas and CRCs. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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“…Then it was found to increase in response to mediators of acute phase response [4] and promote angiogenesis [7]. Thus LRG level was elevated in inflammatory diseases [12] and some cancers [13][14][15]. Recent study also found elevation of LRG is associated with arterial stiffness, endothelial dysfunction, peripheral vascular disease and CAD [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Expression and predictive value of leucine rich α-2 glycoprotein in ischemic heart disease

Gao¹,

Wu²,

Yin³

et al. 2020

Preprint

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Background : The expression and predictive value of leucine rich α-2 glycoprotein (LRG) in ischemic heart disease, including coronary artery disease (CAD), myocardial infarction (MI) and chronic total occlusion (CTO), remain unclear.Methods : A total of 231 patients were included and divided into 4 groups: control group (N=39), CAD group (N=73), MI group (N=67) and CTO group (N=52). LRG was determined and compared within groups. MI group was then divided into 2 subgroups according to LRG expression. The association between LRG expression and clinical characteristics, peak Troponin T (TNT), left ventricular ejection fraction (LVEF) and in-hospital stay was investigated.Results : LRG expression in MI group was significantly higher than that in control group (37.9±12.8 vs 25.3±8.9, P<0.001). LRG expression in CAD and CTO group were similar with that in control group (CAD vs Con, 23.1±6.8 vs 25.3±8.9, P=0.233; CTO vs Con, 22.0±7.8 vs 25.3±8.9, P=0.082). In MI group, patients with increased LRG had higher peak TNT (4.80 (2.34-10.0) vs 2.46 (0.89-4.98), P=0.002), lower LVEF (48.7±10.2 vs 54.8±8.4, P=0.009) and longer in-hospital stay (10.4±5.4 vs 8.0±2.9, P=0.027). Linear regression showed that LRG was independently associated with in-hospital stay. ROC curve showed the area of LRG under the curve (AUC) was 0.859.Conclusions : LRG expression was elevated in MI patients compared with controls, angiography confirmed CAD and CTO patients. In the MI subgroup, patients with elevated LRG had higher peak TNT, lower LVEF and longer in-hospital stay. Whether LRG is associated with major adverse cardiovascular events and long term prognosis needs further investigation.

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Leucine-rich alpha-2-glycoprotein-1 is up-regulated in colorectal cancer and is a tumor promoter

Cited by 33 publications

References 27 publications

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

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

Proteins in stool as biomarkers for non‐invasive detection of colorectal adenomas with high risk of progression

Expression and predictive value of leucine rich α-2 glycoprotein in ischemic heart disease

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