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Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: association with disease recurrence following radical nephrectomy

  • Original Article – Cancer Research
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Abstract

Purpose

To evaluate the expression of multiple molecular markers associated with autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in clear cell renal cell carcinoma (CCRCC) in order to identify the prognostic significance of these markers in patients undergoing radical nephrectomy.

Methods

Expression levels of five markers, including autophagy-related gene 5 (Atg5), Atg9, Beclin 1, microtubule-associated protein light chain 3 (LC3), and UNC-51-like kinase 1 (ULK1), in radical nephrectomy specimens from a total of 100 patients with non-metastatic CCRCC were measured by immunohistochemical staining.

Results

All the five markers were significantly correlated with some pathological factors reflecting an aggressive phenotype, including the pathological T stage, tumor grade, and microvascular invasion. During the follow-up period of this series (median 58.0 months), disease recurrence developed in 41 of the 100 patients, with a 5-year recurrence-free survival (RFS) rate of 61.3 %. On univariate analysis, expression levels of Atg5 and Beclin 1, in addition to the pathological T stage, microvascular invasion, and preoperative CRP level, were identified as significant predictors of disease recurrence. Of these factors, the expression of Beclin 1 and preoperative CRP level were independently correlated with RFS on multivariate analysis.

Conclusion

These findings suggest that the combined assessment of expression levels of autophagy-associated markers, particularly Beclin 1, in radical nephrectomy specimens with conventional prognostic parameters, would contribute to the precise prediction of postoperative disease recurrence in patients with non-metastatic CCRCC.

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Acknowledgments

We thank all the members of Division of Urology, Kobe University Graduate School of Medicine, for helpful discussion.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Masatomo Nishikawa, Hideaki Miyake, Bing Liu & Masato Fujisawa

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  1. Masatomo Nishikawa
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  2. Hideaki Miyake
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  3. Bing Liu
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  4. Masato Fujisawa
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Corresponding author

Correspondence to Hideaki Miyake.

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Nishikawa, M., Miyake, H., Liu, B. et al. Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: association with disease recurrence following radical nephrectomy. J Cancer Res Clin Oncol 141, 1585–1591 (2015). https://doi.org/10.1007/s00432-015-1923-4

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  • DOI: https://doi.org/10.1007/s00432-015-1923-4

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