Polymorphisms of the Stem Cell Marker Gene CD133 and the Risk of Lung Cancer in Chinese Population

Li, Qingfeng; Zhang, Zhifei; Hou, Guangjie; Yang, Guangyu; He, Yi

doi:10.1007/s00408-016-9876-1

Cited by 9 publications

(11 citation statements)

References 22 publications

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“…In contrast, previous studies of rs187116 variation reported that patients with at least one G allele, had an increased risk and recurrence of cancer after gastric surgery in Iran, Japan, North America, and Northeast Thailand (Winder et al, 2011;Bitaraf et al, 2015;Suenaga et al, 2015;Tongtawee et al, 2017). Our study of CD133, rs22406882 (c.*667A>C) shows that the C allele tended to increase the risk of cancer (OR: 1.46; 95% CI: 1.03-2.07; p = 0.033), which is consistent with previous reports that the AC or CC genotypes were associated with increased risk and reduced overall survival rate in lung cancer patients in China (Liu et al, 2016;. However, the variant AC/CC genotypes were associated with decreased risk of gastric cancer (OR: 0.81; 95% CI: 0.67-0.97; p = 0.023) (Jia et al, 2017).…”

Section: Discussionsupporting

confidence: 91%

“…The results showed that the tumor suppressor gene (FOXO3) and proto-oncogene (MDM2) are involved in evading growth suppressors, and the apoptotic genes (caspase 8 and caspase 9) relate to resisting cell death. Moreover, the variation of cancer stem cell marker genes (CD44 rs187116, CD44 rs13347, CD44 rs4756196, CD133 rs3130, CD133 rs2240688, and ALDH1A1), were reported to be associated with an increasing cancer risk (Winder et al, 2011;Jiang et al, 2012;Liu et al, 2016;Lin et al, 2018). The results of this study showed that CD44 rs187116 and CD133 rs2240688 of cancer stem cell marker genes, the inflammatory gene, NF-κB1, and the detoxification gene, GSTM1 were significantly associated with an increased risk of breast cancer (p = 0.041, p = 0.033, p = 0.046, and p = 0.005, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (indel) have potential to indicate risk factors and susceptibility of lung, gastric, and breast cancer (Tan et al, 2010;Park et al, 2012;Eskandari-Nasab et al, 2016;Liu et al, 2016;Deng et al, 2017;Jia et al, 2017). For instance, the rs13347 (c.2392C>T) of CD44 was reported as a predictor marker for breast cancer risk and prognosis (Jiang et al, 2012;Lin et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Previous studies have identified a number of cellular markers which include CD133 (38)(39)(40) and CXCR4 (41,42), that may contribute to the properties exhibited by lung CSCs. Chemokines are a family of small secreted proteins of ~70-80 amino acids.…”

Section: Discussionmentioning

confidence: 99%

CXCR4 is involved in CD133-induced EMT in non-small cell lung cancer

Xie

Xiong

et al. 2016

International Journal of Oncology

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Metastasis is the major cause of death in patients with non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) has been observed to be one of the key regulators of metastasis in certain cancers as it confers an invasive phenotype. CD133 is a widely used cancer stem cell (CSC) marker, and CD133-positive cancer cells are thought to be tumor-initiating cells with CSC characteristics, while CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in NSCLC tissues and participates in cancer progression by regulating cell anti-apoptosis. We previously demonstrated that CXCR4 promotes NSCLC chemoresistance by upregulating CYP1B1, however, the relationship of CD133, CXCR4 and EMT processes in NSCLC metastasis are unclear. In this study, we detected a CD133 and CXCR4 high expression in tissue specimens from 64 NSCLC patients by immunohistochemistry, of which CD133 and CXCR4 were found to be positively associated with metastatic NSCLC patients. CD133 was found to promote NSCLC tumorigenesis and mediated the expression of CXCR4. Furthermore, CD133/CXCR4 co-expression was found to be an independent prognostic factor as shown by univariate and multivariate Cox regression analysis, and was observed to regulate the expression of EMT-related molecules and transcriptional factors in NSCLC. In addition, our results showed that E-cadherin and Vimentin were simultaneously downregulated and upregulated, in CD133+CXCR4+ A549 cells, respectively. While E-cadherin was upregulated and Vimentin was downregulated in metastatic NSCLC patients. Vimentin expression was also observed to have a positive correlation with CD133/CXCR4 co-expression in NSCLC patients and survival analysis results suggested that Vimentin high expression might be significantly associated with poor survival rates of the patients. Thus, these results suggest that the CD133/CXCR4/EMT axis may be a prognostic marker and may provide novel targets for combinational therapies in the treatment of NSCLC.

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“…Stem cells group harboring in tissues of patients with NSCLC were detected by using markers of either ALDH1 or CD133, as were reported and applied before. [28][29][30][31][32][33][34][35] Higher ratios of both ALDH1C cells ( Fig. 1A) and CD133C (Fig.…”

Section: Ratios Of Cancer Stem Cells In Nsclc Correlates With Prognosismentioning

confidence: 99%

miR-367 stimulates Wnt cascade activation through degrading FBXW7 in NSCLC stem cells

Xiao

Zhang

et al. 2017

Cell Cycle

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Lung carcinoma tops the categories of cancer related motility, and has been treated as the main threat to human health. The functions and related mechanism of FBXW7 controlled lung cancer stem cells' signatures is barely unknown, and the miR-367 regulations of FBXW7 via Wnt signaling have not been explored. Cancer stem cells of either ALDH1+ or CD133+ phenotype were found to be referred to advanced stages in patients with NSCLC (non-small cell lung carcinoma). To study the roles of miR-367, we found greater miR-367 level or FBXW7 level was reserved in NSCLC than that of paired adjacent normal tissues, and their upregulations were positively correlated with Wnt signaling activation. On the contrary, increased miR-367 was correlated with Let-7 repression. MiR-367 was related to stronger sphere forming ability in stem cells of NSCLC. We then explored the functions of the endogenous miR-367 in stem-like cells isolated from NSCLC cell lines. In HEK-293 cells, we identified FBXW7 as the direct downstream gene of miR-367, which consequently released the LIN-28 dependent inhibition of suppressive Let-7. Through informatics analysis, miR-367 was predicated to function through Wnt signaling, and decreased Let-7 played the pivotal role to maintain TCF-4/Wnt pathway activity. The reintroduction of FBXW7 abolished the oncogenic stimulation of miR-367 on TCF-4 activity, with Wnt signaling factors depression. In conclusion, our findings demonstrated the oncogenic roles of miR-367 exerting on the self-renewal ability of cancer stem-like cells through degrading the suppressive FBXW7, eventually helping to maintain Wnt signaling activation through a LIN28B/Let-7 dependent manner.

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Polymorphisms of the Stem Cell Marker Gene CD133 and the Risk of Lung Cancer in Chinese Population

Abstract: These findings suggest that SNP rs2240688 A > C of CD133 may be a potential biomarker for genetic susceptibility to lung cancer, but require further research with larger populations.

Cited by 9 publications

References 22 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

CXCR4 is involved in CD133-induced EMT in non-small cell lung cancer

miR-367 stimulates Wnt cascade activation through degrading FBXW7 in NSCLC stem cells

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