title: Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma.
abstract: 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.
authors.affiliation: 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).
authors.forename: Margherita
authors.initials: M
authors.lastname: Gigante
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Divella
authors.forename: Giuseppe Stefano
authors.initials: GS
authors.lastname: Netti
authors.forename: Paola
authors.initials: P
authors.lastname: Pontrelli
authors.forename: Cesira
authors.initials: C
authors.lastname: Cafiero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castellano
authors.forename: Monica
authors.initials: M
authors.lastname: Rutigliano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Carlo
authors.initials: C
authors.lastname: Bettocchi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ditonno
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D012680:Sensitivity and Specificity
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins