Molecular description of <scp>ANGPT2</scp> associated colorectal carcinoma

Jary, Marine; Hasanova, Reyhan; Vienot, Angélique; Asgarov, Kamal; Loyon, Romain; Tirole, Charline; Bouard, Adeline; Orillard, Émeline; Klajer, Elodie; Kim, Stéfano; Viot, Julien; Colle, Elise; Adotévi, Olivier; Bouché, Olivier; Lecomte, Thierry; Borg, Christophe; Feugeas, Jean Paul

doi:10.1002/ijc.32993

Cited by 19 publications

(13 citation statements)

References 52 publications

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“…In contrast, the M2 macrophage stimulated tumor cell migration through the enhanced secretion of a series of proteins that included matrix metalloproteinase 7 (MMP7) and angiopoietin 2 (ANGPT2). These results align with previous reports in the literature regarding the roles of CXCL9, CXCL10 and ANGPT2 [9][10][11][12] and also provide new potential targets (e.g. CXCL11 and MMP7) to limit tumor progression [13,14].…”

Section: Introductionsupporting

confidence: 92%

Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression

Shirure

Liu

et al. 2020

Integrative Biology

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Tumor-infiltrating leukocytes, in particular macrophages, play an important role in tumor behavior and clinical outcome. The spectrum of macrophage subtypes ranges from antitumor ‘M1’-type to protumor ‘M2’-type macrophages. Tumor-associated macrophages (TAMs) typically display phenotypic features of both M1 and M2, and the population distribution is thought to be dynamic and evolves as the tumor progresses. However, our understanding of how TAMs impact the tumor microenvironment remains limited by the lack of appropriate 3D in vitro models that can capture cell–cell dynamics at high spatial and temporal resolution. Using our recently developed microphysiological ‘tumor-on-a-chip’ (TOC) device, we present here our findings on the impact of defined macrophage subsets on tumor behavior. The TOC device design contains three adjacent and connected chambers in which both the upper and lower chambers are loaded with tumor cells, whereas the central chamber contains a dynamic, perfused, living microvascular network. Introduction of human pancreatic or colorectal cancer cells together with M1-polarized macrophages significantly inhibited tumor growth and tumor-induced angiogenesis. Protein analysis and antibody-based neutralization studies confirmed that these effects were mediated through production of C-X-C motif chemokines (CXCL9), CXCL10 and CXCL11. By contrast, M2-macrophages mediated increased tumor cell migration into the vascularized chamber and did not inhibit tumor growth or angiogenesis. In fact, single-cell RNA sequencing showed that M2 macrophages further segregated endothelial cells into two distinct subsets, corresponding to static cells in vessels versus active cells involved in angiogenesis. The impact of M2 macrophages was mediated mostly by production of matrix metalloproteinase 7 and angiopoietin 2. In summary, our data demonstrate the utility of the TOC device to mechanistically probe biological questions in a 3D in vitro microenvironment.

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Section: Introductionsupporting

confidence: 92%

Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression

Shirure

Liu

et al. 2020

Integrative Biology

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“…Among the 35 eligible studies were 27 full-text articles ( 6 , 11 , 12 , 15 , 55–77 ) and 8 conference abstracts ( 78–85 ). Prognostic data were extracted from 21 studies, of which 2 were conference abstracts ( 6 , 11 , 15 , 57 , 58 , 60 , 61 , 63 , 64 , 66–73 , 75 , 77 , 80 , 81 ). The predictive value of the CMSs was assessed in 16 studies and 6 conference abstracts ( 12 , 15 , 55–57 , 59 , 62 , 64–67 , 69 , 72–74 , 76 , 78 , 79 , 82–85 ).…”

Section: Resultsmentioning

confidence: 99%

“…The meta-analyses into the prognostic value of the CMSs in local disease included patients from 11 cohorts. We found worse OS for CMS4 compared with CMS1 (stage I-III: HR = 3.28, 95% CI = 1.27 to 8.47; number of included cohorts [n] = 4) ( 15 , 61 , 66 , 70 ) and for CMS4 compared with CMS2 (stage I-III: HR = 2.60, 95% CI = 1.93 to 3.50; n = 3) ( 11 , 70 ). The same pattern was observed for the RFS and SAR ( Figure 2, A and B ) ( 11 , 58 , 70–72 , 75 ).…”

Section: Resultsmentioning

confidence: 99%

Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis

Hoorn

Back

Sommeijer

et al. 2021

JNCI: Journal of the National Cancer Institute

113

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Background The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs. Methods We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized. Results In local disease, CMS4 tumors were associated with worse overall survival (OS) compared to CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval= 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33 to 0.55; progression-free survival HR range = 0.53 to 0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16 to 0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome as compared to oxaliplatin (HR range = 0.31 to 0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-EGFR therapy improved outcome for KRAS wildtype CMS2 patients. Conclusions The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.

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“…Some studies had shown that the relative expression level of the STC1 gene in cancer tissues was higher than that in adjacent normal mucosa; the high expression of STC1 was associated with a low postoperative survival rate. STC1 and other genes constitute a molecular network, which endows CRC with chemoresistance ( Tamura et al, 2011 ; Jary et al, 2020 ).VIP can regulate the growth and function of various immune cells and tumor cells. Compared with normal blood cells and other mesenchymal cells, various tumor cells, including colonic adenocarcinoma, pancreatic cancer, and carcinoid, express a large number of VIP receptors ( Virgolini et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Model Using Immune-Related Genes for Colorectal Cancer

Wei

Zhang

Liu

et al. 2022

Front. Cell Dev. Biol.

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There is evidence suggesting that immune genes play pivotal roles in the development and progression of colorectal cancer (CRC). Colorectal carcinoma patient data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were randomly classified into a training set, a test set, and an external validation set. Differentially expressed gene (DEG) analyses, univariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) were used to identify survival-associated immune genes and develop a prognosis model. Receiver operating characteristic (ROC) analysis and principal component analysis (PCA) were used to evaluate the discrimination of the risk models. The model genes predicted were verified using the Human Protein Atlas (HPA) databases, colorectal cell lines, and fresh CRC and adjacent tissues. To understand the relationship between IRGs and immune invasion and the TME, we analyzed the content of immune cells and scored the TME using CIBERSORT and ESTIMATE algorithms. Finally, we predicted the potential sensitive chemotherapeutic drugs in different risk score groups by the Genomics of Drug Sensitivity in Cancer (GDSC). A total of 491 IRGs were screened, and 14 IRGs were identified to be significantly related to overall survival (OS) and applied to construct an immune-related gene (IRG) prognostic signature (IRGSig) for CRC patients. Calibration plots showed that nomograms have powerful predictive ability. PCA and ROC analysis further verified the predictive value of this fourteen-gene prognostic model in three independent databases. Furthermore, we discovered that the tumor microenvironment changed significantly during the tumor development process, from early to middle to late stage, which may be an essential factor for tumor deterioration. Finally, we selected six commonly used chemotherapeutic drugs that have the potential to be useful in the treatment of CRC. Altogether, immune genes were used to construct a prognosis model for CRC patients, and a variety of methods were used to test the accuracy of this model. In addition, we explored the immune mechanisms of CRC through immune cell infiltration and TME in CRC. Furthermore, we assessed the therapeutic sensitivity of many commonly used chemotherapeutic medicines in individuals with varying risk factors. Finally, the immune risk model and immune mechanism of CRC were thoroughly investigated in this paper.

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Molecular description of ANGPT2 associated colorectal carcinoma

Cited by 19 publications

References 52 publications

Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression

Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression

Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis

A Prognostic Model Using Immune-Related Genes for Colorectal Cancer

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