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The serum level of the components of the renin-angiotensin system correlates with its tumor tissue expression in kidney cancer patients

  • Roman Osokin,
  • Ekaterina Komarova,
  • Igor Aboyan,
  • Aleksey Yu. Maksimov,
  • Natalya D. Ushakova,
  • Roman Ischenko,
  • Olga Shatova,
  • Elizaveta Komarova

Research Funding
None

Background
To date, it has not been decided whether the locally-generated components of the renin-angiotensin system (RAS) involved in the pathogenesis of kidney cancer and arterial hypertension, and are local and systemic RAS related? The aim was to assess the relationship of the level of RAS in the tumor tissue and peripheral blood in patients with localized kidney cancer with arterial hypertension.

Methods
In patients with localized kidney cancer T1N0M0 (KС) and arterial hypertension of the I-II stage (AH), tissue and serum levels of angiotensin I, angiotensin II, angiotensin (1-7), as well as angiotensin converting enzymes (ACE and ACE2) were determined in the following groups: patients with KC without AH (n = 35, KC) and with concomitant AH (n = 30; KC+ AH). The normative values of peripheral blood indices were revealed in healthy donors (n = 30).

Results
The level of all studied RAS peptides in the serum of patients with KC was increased in comparison with healthy donors regardless of concomitant hypertension, and the activity of both circulating angiotensin-converting enzymes, on the contrary, was increased only in patients with hypertension. The level of AT1 exceeds the control indicators by 1.7 times (KC) and 2.8 times (KC + AH). The formation of AT2 is higher in the KC + AH compared to KC (2.2 times versus 1.7 times, at p < 0.05). The content of AT (1-7) significantly exceeds the control (1.3 times on average, p < 0.05) and higher in the KC + AH. Increased enzyme activity was detected in KC + AG: increased by 1.5 times (p < 0.05) and 1.7 (p < 0.05) compared with the control for ACE and ACE2, respectively. The pair correlation coefficients between the serum RAS and the studied tissues in the KC were: for AT1 -0.78/0.65; АТ2-0.64/0.59 and АТ (1-7) – 0.56/0.51; ACE2 0.55/0.65 (for tumor/peritumoral tissue: in all cases at p < 0.05). In the KC+AH, these ratios were: for AT1 -0.85/0.81; АТ2-0.72/0.74 and АТ (1-7) – 0.65/0.59; ACE2 0.61/0.52 (for tumor / peritumoral tissue: in all cases at p < 0.05).

Conclusions
The serum content of RAS peptides had positive statistical relationships with the corresponding parameters in tumor and peritumoral tissues of kidney cancer pts. However, in hypertensive patients with kidney cancer the correlations found had a tightness of higher strength. Positive correlations of the level of locally generated tumor parameters of RAS with their circulating analogues indicate the possibility of their use as diagnostic markers of the development of kidney cancer.