Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype.
The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0. 01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0. 003), Fuhrman grade (P = 0. 007), and clinical stage (P = 0. 0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0. 0001 and P = 0. 0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2. 11; P = 0. 03) and PFS (HR = 2. 18; P = 0. 03). These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis.
Medicine. 2015 Nov [Epub]
Margherita Gigante, Giuseppe Lucarelli, Chiara Divella, Giuseppe Stefano Netti, Paola Pontrelli, Cesira Cafiero, Giuseppe Grandaliano, Giuseppe Castellano, Monica Rutigliano, Giovanni Stallone, Carlo Bettocchi, Pasquale Ditonno, Loreto Gesualdo, Michele Battaglia, Elena Ranieri
From the Department of Emergency and Organ Transplantation - Nephrology, Dialysis and Transplantation Unit (MG, CD, CC, PP, GC, LG); Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari (GL, MR, CB, PD, MB); Department of Medical and Surgical Sciences, Clinical Pathology, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy (GG, GS, ER).