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Reduced expression of CXCR4, a novel renal cancer stem cell marker, is associated with high-grade renal cell carcinoma

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Cancer stem cells (CSCs) represent a population with tumour-initiating, self-renewal, and differentiation potential. This study aimed to evaluate the expression patterns and clinical significance of chemokine receptor type 4 (CXCR4) as a novel CSC marker in renal cell carcinoma (RCC).

Methods

The expression of CXCR4 was examined in 173 well-defined renal tumour tissues, including 106 (61.5 %) clear cell renal cell carcinomas (ccRCCs), 35 (20 %) papillary renal cell carcinomas (pRCCs), and 32 (18.5 %) chromophobe renal cell carcinomas (ChRCCs), by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters was then analysed.

Results

There was a significant difference in the expression levels of CXCR4 in the ccRCC samples compared to the ChRCC and pRCC samples (P < 0.001). Increased expression of CXCR4 was significantly correlated with higher-grade tumours (P < 0.001) and worse stage (P = 0.001). A significant association was also found between expression of CXCR4 and microvascular invasion (P = 0.018). Among RCC subtypes, comparison of the differences between CXCR4 expression in low- and high-grade tumours demonstrated that pRCC tumours had a significantly higher expression of CXCR4 (P < 0.001) than ccRCC tumours (P = 0.01).

Conclusion

Significantly higher expression levels of CXCR4 were found in pRCC and ccRCC samples. Increased CXCR4 expression was associated with more aggressive tumour behaviour in RCC patients, especially in pRCC and ccRCC subtypes due to their more metastatic behaviour. These findings suggest that CXCR4 can be considered as a novel diagnostic and therapeutic marker for targeted therapy of renal carcinoma.

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Acknowledgments

This study was supported by a grant from Iran University of Medical Sciences (Grant #25166). The authors are grateful to Elham Kalantari for her excellent technical assistance.

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Authors and Affiliations

  1. Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran, 14496-14530, Iran

    Arezoo Rasti, Maryam Abolhasani, Leili Saeednejad Zanjani, Mojgan Asgari, Mitra Mehrazma & Zahra Madjd

  2. Hasheminejad Kidney Center, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Maryam Abolhasani, Mojgan Asgari & Mitra Mehrazma

  3. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Zahra Madjd

Authors
  1. Arezoo Rasti
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  2. Maryam Abolhasani
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  3. Leili Saeednejad Zanjani
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  4. Mojgan Asgari
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  5. Mitra Mehrazma
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  6. Zahra Madjd
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Correspondence to Mitra Mehrazma or Zahra Madjd.

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The authors declare no conflict of interest.

Ethical approval

The study was approved by the Iran University of Medical Sciences. All procedures performed in this study were in accordance with the 1964 Helsinki Declaration and its later amendments.

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Rasti, A., Abolhasani, M., Zanjani, L.S. et al. Reduced expression of CXCR4, a novel renal cancer stem cell marker, is associated with high-grade renal cell carcinoma. J Cancer Res Clin Oncol 143, 95–104 (2017). https://doi.org/10.1007/s00432-016-2239-8

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  • DOI: https://doi.org/10.1007/s00432-016-2239-8

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