The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer.
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.


OBJECTIVE
We undertook this study to evaluate the prognostic value of KLK8 in ovarian carcinoma by examining its expression in ovarian tumors.


METHODS
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.
Magklara
A
A
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, M5G 1X5 Canada.
Scorilas
A
A
Katsaros
D
D
Massobrio
M
M
Yousef
G M
GM
Fracchioli
S
S
Danese
S
S
Diamandis
E P
EP
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007610:Kallikreins; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics* / Q000302:isolation & purification
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C094799:KLK8 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases