Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer

Aravantinos, G.; Isaakidou, Athina; Karantanos, Theodoros; Sioziou, Anna; Théodoropoulos, Georgios; Pektasides, Dimitrios; Gazouli, Maria

doi:10.3233/cbm-150528

Cited by 10 publications

(7 citation statements)

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“…The other polymorphisms including detoxification genes (GSTT1), cancer stem cell marker genes (CD44 rs13347, CD44 rs4756196, CD133 rs3130, and ALDH1A1), apoptotic genes (caspase 8 and caspase 9), growth factor genes (TGFβ2 and VEGF), tumor suppressor gene (FOXO3), and proto-oncogene (MDM2) did not show an association with breast cancer in this study, indicating that these polymorphisms do not necessarily increase the risk of breast cancer in our population. However, these genes were reported to be associated with other cancers, such as nasopharyngeal, gastric, lung, and colorectal cancer (Son et al, 2006;Xiao et al, 2013;Aravantinos et al, 2015;Jia et al, 2017). The genetic background of the population might be the cause of this discrepancy.…”

Section: Discussionmentioning

confidence: 99%

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand

Sapcharoen

Sanguansermsri

Yasothornsrikul

et al. 2019

Asian Pac J Cancer Prev

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Background:Biomarkers play an important role in oncology, including risk assessment, treatment prediction, and monitoring the progression of disease. In breast cancer, many genes are used as biomarkers. Since, several SNP variations of hallmark – related genes have been reported to be of value in risk prediction in various cancers and populations, some genetic polymorphism loci were combined and reported as biomarkers for use in the risk assessment of breast cancer in Thai people. Methods:Twelve cancer gene hallmarks (15 polymorphic loci) were selected and genotyped in 184 breast cancer patients and 176 healthy individuals in Phitsanulok, Thailand. Results:AA genotype of CD44 rs187116 (c.67+4883G>A), the C allele of CD133 rs2240688 (c.*667A>C), the *2 allele (4 bp deletion) of NF-κB1 rs28362491 and the homozygous null allele genotype of GSTM1 were significantly associated with an increased risk of breast cancer (p<0.05). A combination of these 4 significant loci showed that AA-AA-*1*1-homozygous null allele genotype has the greatest correlation with increased risk of breast cancer (OR = 21.00; 95% CI: 1.77 to 248.11; p = 0.015), followed by GA-AA-*2*2- homozygous null allele genotype (p = 0.037) and GG-AC-*1*2- homozygous null allele genotype (p = 0.028). Conclusion:These findings suggest that the polymorphisms of CD44 rs187116 (c.67+4883G>A), CD133 rs2240688 (c.*667A>C), NF-κB1 rs28362491 and GSTM1 homozygous null allele genotype might be associated with an increased risk of breast cancer, and this gene combination could possibly be used as biomarkers for risk prediction, which would be of benefit in planning health surveillance and cancer prevention.

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Section: Discussionmentioning

confidence: 99%

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand

Sapcharoen

Sanguansermsri

Yasothornsrikul

et al. 2019

Asian Pac J Cancer Prev

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“…Recruitment of CD133 + pro-angiogenic cells in cancer has been considered to play an important role in resistance to vascular growth factor (VEGF) neutralizing antibody such as bevacizumab, possibly due to failure to inhibit their differentiation into endothelial cell types [ 54 ]. Moreover, CD133 gene polymorphism have been associated with lower overall survival rate in patients treated with bevacizumab in metastatic colorectal cancer treated [ 55 ]. These studies generally have as their premise that VEGF as a tumor angiogenic factor.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 2-signaling in CD133-expressing cells in renal clear cell carcinoma

et al. 2016

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Compared to normal kidney, renal clear cell carcinomas (ccRCC) contain increased numbers of interstitial, non-hematopoietic CD133+cells that express stem cell markers and exhibit low rates of proliferation. These cells fail to form tumors upon transplantation but support tumor formation by differentiated malignant cells. We hypothesized that killing of ccRCC CD133+ (RCCCD133+) cells by cytotoxic agents might be enhanced by inducing them to divide. Since tumor necrosis factor-alpha (TNF), signalling through TNFR2, induces proliferation of malignant renal tubular epithelial cells, we investigated whether TNFR2 might similarly affect RCCCD133+cells. We compared treating organ cultures of ccRCC vs adjacent nontumour kidney (NK) and RCCCD133+ vs NK CD133+ (NKCD133+) cell cultures with wild-type TNF (wtTNF) or TNF muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF). In organ cultures, R2TNF increased expression of TNFR2 and promoted cell cycle entry of both RCCCD133+ and NKCD133+ but effects were greater in RCCCD133+. In contrast, R1TNF increased TNFR1 expression and promoted cell death. Importantly, cyclophosphamide triggered much more cell death in RCCCD133+ and NKCD133+cells pre-treated with R2TNF as compared to untreated controls. We conclude that selective engagement of TNFR2 by TNF can drives RCCCD133+ proliferation and thereby increase sensitivity to cell cycle-dependent cytotoxicity.

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“…This may be attributed to the fact that CD133 expression is closely related to cell proliferation, apoptosis, invasion and metastasis, and angiogenesis (39)(40)(41)(42). Furthermore, it has been shown that SNPs located in the 3'untranslated region (3'-UTR) region of the CD133 gene are associated with a variety of human tumors (38,43,44). SNPs in the 3'-UTR have also been shown to have functional effects on the control of mRNA stability and efficiency through the regulation of miRNA, including miR-34a, -101, -128, -137 and -1385 (45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

SNP rs2240688 in CD133 gene on susceptibility and clinicopathological features of hepatocellular carcinoma

Pan¹,

Huang²,

Mo³

et al. 2020

Transl Cancer Res TCR

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Background: CD133 is one of the important cancer stem cells (CSCs) markers of hepatocellular carcinoma (HCC). The aim of this study was to explore the relationship between CD133 single-nucleotide polymorphisms (SNPs) and risk factors associated with HCC susceptibility and clinicopathological features in HCC cases and healthy controls from the Guangxi region of southern China.Methods: A case control study was conducted, including 565 HCC patients and 561 control subjects. The genotyping of rs2240688 was performed using the SNaPshot method. Unconditional logistic regression was used to correct for gender, age, and other confounding factors. Odds ratio (OR) and its 95% confidence interval (CI) were calculated to analyze the relationship between allele and genotype frequency and the risk of HCC. Results:The distribution frequencies of CD133 alleles and genotypes in the HCC case group and the control group were statistically significant (P<0.05). The CA heterozygous (P=0.003, OR =1.463, 95% CI: 1.134-1.887) and CC homozygous genotypes (P=0.036, OR =1.910, 95% CI: 1.044-3.493), as well as C carrier status (P=0.004, OR =1.465, 95% CI: 1.136-1.889) and C alleles (P=0.004, OR =1.465, 95% CI: 1.136-1.889), were associated with an increased risk of HCC. Additionally, in the subgroup analysis of CD133 rs2240688 polymorphism and clinical characteristics, the results showed that the genotype distribution of CD133 rs2240688 was significantly different in genotype distribution of metastasis and alanine aminotransferase (ALT).Conclusions: the expression of miRNA binding site rs2240688 of tumor stem cell marker gene CD133 in HCC may be a promising marker for the prediction of HCC, but larger studies are still needed.

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Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer

Abstract: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot be attributed to increased treatment toxicity.

Cited by 10 publications

References 0 publications

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand

Tumor necrosis factor receptor 2-signaling in CD133-expressing cells in renal clear cell carcinoma

SNP rs2240688 in CD133 gene on susceptibility and clinicopathological features of hepatocellular carcinoma

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