Klotho expression in epithelial ovarian cancer and its association with insulin-like growth factors and disease progression.
Klotho is an anti-aging hormone and is able to suppress the action of IGFs. High IGF activities are associated with cancer risk and tumor progression. Klotho's role in cancer is unknown. To evaluate Klotho expression in ovarian cancer and its association with IGFs and ovarian cancer progression, a clinical follow-up study of 189 ovarian cancer patients was conducted. Patients were recruited from a teaching hospital at University of Turin in Italy. All patients were diagnosed with epithelial ovarian cancer and underwent surgery for the disease. Fresh tumor tissue was collected from each patient during surgery. Patient clinical and pathological information was collected, including patient age at surgery, disease stage, tumor grade, tumor histology, residual tumor size, debulking result, post-operative chemotherapeutic agent, treatment response, follow-up time and survival outcome. Expressions of total and secreted Klotho as well as IGFs in tumor tissue were analyzed using quantitative real-time PCR. Survival analysis was performed to evaluate the association of Klotho expression with the risk of disease progression and death using Cox proportional hazards regression model. High expression of secreted Klotho was associated with increased risk of disease progression and death. These associations were independent of patient clinical and pathological characteristics. Expression of secreted Klotho was positively correlated with the expression of IGF-I and IGFBP-3 but not with IGF-II. In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho's role in cancer warrants further elucidation.
Lu
Lingeng
L
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
Katsaros
Dionyssios
D
Wiley
Andrew
A
de la Longrais
Irene A Rigault
IA
Puopolo
Manuela
M
Yu
Herbert
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D000090265:Klotho Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D012334:RNA, Neoplasm; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005966:Glucuronidase; D000090265:Klotho Proteins