CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy

Matsusaka, Satoshi; Cao, Shu; Hanna, Diana L.; Sunakawa, Yu; Ueno, Masashi; Mizunuma, Nobuyuki; Zhang, W; Yang, Dongyun; Ning, Yan; Stintzing, Sebastian; Sebio, Ana; Stremitzer, Stefan; Yamauchi, Shinichi; Parekh, Anish; Okazaki, Satoshi; Berger, Martin D.; El-Khoueiry, Rita; Mendez, Angela; Ichikawa, Wataru; Loupakis, Fotios; Hj, Lenz

doi:10.1038/tpj.2016.59

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…There are several studies which have also shown that SNP polymorphisms can be effective in the advancing and development of other cancers [ 47 , 48 ] and the present study. These studies indicate the importance of examining the association of the polymorphism of some genes with the progression of cancer.…”

Section: Discussionsupporting

confidence: 70%

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer

Dehghani

Samani

Abidi

et al. 2018

International Journal of Genomics

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Background and Purpose The mevalonate pathway is one of the major metabolic pathways that use acetyl-CoA to produce sterols and isoprenoids. These compounds can be effective in the growth and development of tumors. One of the enzymes involved in the mevalonate pathway is FDFT1. Different variants of this gene are involved in the risk of suffering various diseases. The present study examined the relationship between FDFT1 rs2645429 polymorphism and the risk of nonsmall cell lung cancer (NSCLC) in a population from southern Iran. Method The genotypes of rs2645429 polymorphism of FDFT1 gene were examined in 95 samples: 34 patients with NSCLC and 61 healthy individuals by RFLP method. Results The results of this study indicated that C allele of this polymorphism was effectively associated with the risk of NSCLC in the Iranian population (p value = 0.023; OR = 2.71; 95% CI = 1.12–6.59) and CC genotype has significant relation with susceptibility to NSCLC (p value = 0.029; OR = 3.02; 95% CI = 1.09–8.39). This polymorphism is located in the promoter region FDFT1 gene, and CC genotype may increase the activity of this promoter. This study also found a significant relationship between C allele and metastatic status. C allele was more common in NSCLC patients. (p = 0.04). Conclusion C allele of FDFT1 rs2645429 polymorphism gene can be a risk factor for NSCLC, whereas T allele probably has a low protective role.

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Section: Discussionsupporting

confidence: 70%

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer

Dehghani

Samani

Abidi

et al. 2018

International Journal of Genomics

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“…The results showed that MERTK and SYK were druggable according to the CIViC database (18,36,37). Gene variations in CXCR4, FCGR2A, MGAT4A, NCOA1, PIK3R1, RGS5, RRAS2 and SOD2 may be predictive markers or have targetable variations according to the PharmGKB database (16,38–47). A total of 10 oncogenes ( CXCR4, ERG, FLT1, IGF1, KDR, LYN, MITF, PIK3CG, REL and SYK ), six tumor suppressor genes ( MITF, MAP3K1, MOB3B, NFKBIA, PRDM1 and SAMHD1 ) and one gene (CSF1R), belonging to neither oncogene or tumor suppressor gene categories, were identified, according to the oncoKB database.…”

Section: Resultsmentioning

confidence: 99%

Identification of key genes in osteosarcoma by meta‑analysis of gene expression microarray

Sun

et al. 2019

Mol Med Report

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Osteosarcoma (OS) is one of the most malignant tumors in children and young adults. To better understand the underlying mechanism, five related datasets deposited in the Gene Expression Omnibus were included in the present study. The Bioconductor ‘limma’ package was used to identify differentially expressed genes (DEGs) and the ‘Weighted Gene Co-expression Network Analysis’ package was used to construct a weighted gene co-expression network to identify key modules and hub genes, associated with OS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes overrepresentation analyses were used for functional annotation. The results indicated that 1,405 genes were dysregulated in OS, including 927 upregulated and 478 downregulated genes, when the cut off value was set at a ≥2 fold-change and an adjusted P-value of P<0.01 was used. Functional annotation of DEGs indicated that these genes were involved in the extracellular matrix (ECM) and that they function in several processes, including biological adhesion, ECM organization, cell migration and leukocyte migration. These findings suggested that dysregulation of the ECM shaped the tumor microenvironment and modulated the OS hallmark. Genes assigned to the yellow module were positively associated with OS and could contribute to the development of OS. In conclusion, the present study has identified several key genes that are potentially druggable genes or therapeutics targets in OS. Functional annotations revealed that the dysregulation of the ECM may contribute to OS development and, therefore, provided new insights to improve our understanding of the mechanisms underlying OS.

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“…A common CXCR4 polymorphism (rs2228014 C/C genotype) has recently been found to predict progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy. 52 The nucleotide sequence of the CXCR4 gene and 350-bp upstream regulatory region from CT-2A and GL261 glioma genomic DNA was analyzed by Sanger sequencing of PCR-amplified products, but no CXCR4 mutations were identified in glioma cells that could alter their function or response to the treatments ( Figure 6 and Table 1).…”

Section: Cxcr4 Gene Mutation Analysis In Glioma Cellsmentioning

confidence: 99%

Multifaceted C-X-C Chemokine Receptor 4 (CXCR4) Inhibition Interferes with Anti–Vascular Endothelial Growth Factor Therapy–Induced Glioma Dissemination

Gagner

Sarfraz

Ortenzi

et al. 2017

The American Journal of Pathology

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Resistance to antiangiogenic therapy in glioblastoma (GBM) patients may involve hypoxia-induced expression of C-X-C motif chemokine receptor 4 (CXCR4) on invading tumor cells, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with POL5551 disrupts anti-vascular endothelial growth factor (VEGF) therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-VEGF antibody B20-4.1.1. Brain tissue was analyzed for tumor volume, invasiveness, hypoxia, vascular density, proliferation, apoptosis, GSCs, and MGCs. Glioma cells were evaluated for CXCR4 expression and polymorphism and POL5551's effects on CXCR4 ligand binding, cell viability, and migration. No CXCR4 mutations were identified. POL5551 inhibited CXCR4 binding to its ligand, stromal cell-derived factor-1α, and reduced hypoxia- and stromal cell-derived factor-1α-mediated migration dose-dependently but minimally affected cell viability. In vivo, B20-4.1.1 increased hypoxic foci and invasiveness, as seen in GBM patients receiving anti-VEGF therapy. Combination of POL5551 and B20-4.1.1 reduced both glioma invasiveness by 16% to 39% and vascular density compared to B20-4.1.1 alone in both glioma models. Reduced populations of GSCs and MGCs were also seen in CT-2A tumors. POL5551 concentrations, evaluated by mass spectrometry, were higher in tumors than in neighboring brain tissues, likely accounting for the results. Inhibition of CXCR4-regulated tumoral, stem cell, and immune mechanisms by adjunctive CXCR4 antagonists may help overcome antiangiogenic therapy resistance, benefiting GBM patients.

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CXCR4 polymorphism predicts progression-free survival in metastatic colorectal cancer patients treated with first-line bevacizumab-based chemotherapy

Cited by 11 publications

References 31 publications

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer

Identification of key genes in osteosarcoma by meta‑analysis of gene expression microarray

Multifaceted C-X-C Chemokine Receptor 4 (CXCR4) Inhibition Interferes with Anti–Vascular Endothelial Growth Factor Therapy–Induced Glioma Dissemination

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