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Molecular Oncology, Markers, Clinical Correlates |
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1X5 Canada [A. M., A. S., G. M. Y., E. P. D.], and Departments of Obstetrics and Gynecology, Gynecologic Oncology Unit [D. K., M. M., S. F.] and Gynecology, S. Anna Hospital [S. D.], University of Turin, Turin 10126, Italy
KLK8 (neuropsin/ovasin) is a new member of the human kallikrein gene family, which consists of enzymes with serine protease enzymatic activity. Recent reports have implicated KLK8 in ovarian cancer. KLK8 may have potential clinical value for disease diagnosis or prognosis and it may also be a useful therapeutic target.
Purpose: We undertook this study to evaluate the prognostic value of KLK8 in ovarian carcinoma by examining its expression in ovarian tumors.
Experimental Design: The KLK8 gene was analyzed by reverse transcription-PCR and direct sequencing in several human normal tissues. Subsequently, its expression was studied in a set of ovarian tumors, and statistical analysis was performed.
Results: We have identified two novel mRNA splice variants of the KLK8 gene, which are abundantly expressed in many tissues. These new variants were named KLK8 type 3 and type 4. Study of the expression of the KLK8 gene and its spliced variants in ovarian tumors indicated that the new variants were expressed very frequently and that full-length KLK8 expression is an independent and favorable prognostic marker for ovarian cancer. Patients with higher KLK8 expression in the tumor have lower grade disease, lower residual tumor left after surgery, live longer, and relapse less frequently. In multivariate analysis, higher KLK8 expression was significantly associated with longer disease-free survival.
Conclusions: These results suggest that KLK8 is a novel, favorable prognostic marker in ovarian cancer. Because KLK8 encodes for a predicted secreted protein, its detection in serum may aid in ovarian cancer diagnosis.
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