Metastasis suppressor kisspeptin (KISS1) in serum of patients with renal cell carcinoma

Abstract

Background. The most important problems in improvement of treatment outcomes in patients with renal cell carcinoma (RCC) are search and validation of molecular markers for its early diagnosis and prognosis. Genes suppressing distant metastasizing but not affecting the primary tumor are called metastasis suppressors. Study of these genes and their products not only improves understanding of the mechanisms of tumor progression, but has practical value for diagnosis, prognosis, and establishment of new molecular targets for antitumor therapy. One of such genes is KISS1 with its product kisspeptin (KISS1) protein.Aim: comparative evaluation of KISS1 concentration in blood serum of practically healthy persons and patients with renal cancer; analysis of correlations between the marker’s level and clinical and morphological characteristics of the disease.Materials and methods. 140 patients with RCC (88 men, 52 women) aged between 29 and 82 years were included in the study. Among them, clear cell RCC was diagnosed in 84 patients, papillary in 38, chromophobe in 18. The control group was comprised of 40 healthy persons of matched age and sex. Pre-treatment KISS1 concentration in blood serum was measured using a direct enzyme immunoassay kit (Kisspeptin 1 – KISS1, Cloud-Clone Corp., USA).Results. Median serum KISS1 concentration in the control group was 51.7 pg/mL which was significantly lower than in the total RCC patient group – 243.6 pg/mL (p <0.0001). ROC analysis of diagnostic value of serum KISS1 level was performed both for the total RCC group and for each of its three histological types. In the total group the sensitivity of the test was 75 %, specificity – 80 % (AUC 0.877; 95 % confidence interval (CI) 0.827–0.927; optimal cut-off level 130.8 pg/mL; р <0.0001). For clear cell RCC, both sensitivity and specificity were 85 % (AUC 0.941; 95 % CI 0.902– 0.979; cut-off 141.8 pg/mL; p <0.0001). In non-clear cell RCC types, sensitivity of this marker was only 58 % while the specificity remained 80 % (for papillary RCC AUC 0.787; 95 % CI 0.684–0.889; cut-off level 135.5 pg/mL; p <0.0001, and for chromophobe RCC AUC 0.774; 95 % CI 0.617–0.929; cut-off level 132.1 pg/mL; p <0.001). KISS1 level increased with disease progression: it is significantly higher at more advanced stages above stage I, and in patients with distant metastases compared to those without metastases. Higher serum KISS1 level is also observed in patients with poorly differentiated high-grade (per Furhman) clear cell RCC and papillary RCC (G3–G4) than in those with well differentiated low-grade (G1–G2) tumors.Conclusion. KISS1 level is significantly increased in patients with RCC compared to healthy controls and is a stagedependent marker of this disease. It has relatively high diagnostic sensitivity and specificity (both 85 %) for the most frequent histological type of RCC – clear cell RCC. Thus, clinical significance of kisspeptin in RCC requires further investigation.