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Basic and translational research
Original research article
Elevated serum levels of cardiovascular biomarkers are associated with progression of renal cancer
  1. Takao Kamai,
  2. Yuumi Tokura,
  3. Toshitaka Uematsu,
  4. Kazumasa Sakamoto,
  5. Issei Suzuki,
  6. Kohei Takei,
  7. Takahiro Narimatsu,
  8. Tsunehito Kambara,
  9. Hideo Yuki,
  10. Hironori Betsunoh,
  11. Hideyuki Abe,
  12. Yoshitatsu Fukabori,
  13. Masahiro Yashi and
  14. Ken-Ichiro Yoshida
  1. Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan
  1. Correspondence to Dr Takao Kamai, Department of Urology Dokkyo Medical University Mibu Tochigi Japan ; kamait{at}dokkyomed.ac.jp

Abstract

Objective Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed.

Methods In patients with clear cell RCC who underwent nephrectomy, we investigated the relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and various clinicopathological characteristics, including serum VEGF and expression of BNP and HIF-2 alpha in the primary tumour.

Results Elevated preoperative serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression of HIF-2 alpha, were associated with a worse performance status, local invasion, distant metastasis and shorter overall survival. HIF-2 alpha expression showed a positive correlation with the preoperative serum VEGF level, while there was no relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased significantly after nephrectomy.

Conclusions Our findings suggested that the preoperative serum levels of BNP and NT-proBNP are markers of tumour progression, as well as indicators of subclinical functional and structural myocardial damage in patients with advanced RCC.

  • heart failure with normal ejection fraction
  • cytokines
  • malignancy

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2017-000666

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    Footnotes

    • Contributors TK initiated the study, participated in its design and coordination, carried out the study, performed the statistical analysis and drafted the manuscript. YT, TU, KS, IS, KT, TN, TK, HY, HB, HA, YF and MY carried out the study. KIY participated in the design of the study and helped draft the manuscript. All authors read and approved the final manuscript.

    • Funding The study was funded by Japanese Science Progress Society KAKENHI (17K11156).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval This study was conducted in accordance with the Helsinki Declaration and was approved by the institutional Ethical Review Board of Dokkyo Medical University Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices).