Prognostic value of quantitatively assessed KLK7 expression in ovarian cancer.
BACKGROUND
Among females, ovarian cancer is the sixth most common malignancy. Women with ovarian cancer have poor overall survival rates, largely because the disease is often diagnosed at an advanced, less curable stage. Several lines of evidence suggest that members of the kallikrein family are involved in various malignancies such as prostate (PSA, KLK2, KLK15), ovarian (KLK4, KLK5, KLK6, KLK8, KLK10), and breast cancer (KLK10, KLK13, KLK14). Recent evidence has indicated that expression of KLK7 appears to be increased in ovarian cancer. We hypothesized that overexpression of the KLK7 gene in ovarian cancer may serve as a prognostic marker of the disease.


METHODS
Using the LightCycler technology we quantified the level of KLK7 mRNA expression in 125 ovarian tumors. Different disease stages and tumor grades were analyzed. Univariate and multivariate analyses were performed to establish the associations between clinicopathological parameters and KLK7 expression.


RESULTS
We here report that patients with KLK7-negative tumors have a significantly higher disease-free survival than patients with KLK7-positive tumors. KLK7 expression levels were significantly higher in patients with grade 3 than in patients with grade 1 to 2 tumors (p = 0.030). KLK7 status also correlated with size of residual tumor postsurgery. KLK7 expression is an independent predictor of both disease-free and overall survival for patients with low grade tumors. In this subgroup of patients the hazard ratios for disease-free and overall survival were 3.28 and 3.09, respectively. Similarly, patients who had undergone optimal debulking but harbored KLK7-positive tumors had a high hazard ratio (HR) for relapse (HR = 8.2) and death (HR = 4.6).


CONCLUSIONS
We conclude that higher KLK7 expression in ovarian cancer tissue is associated with poorer prognosis of ovarian cancer patients, especially those with lower grade disease and those who have been optimally debulked.
Kyriakopoulou
Lianna G
LG
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1X5 Canada.
Yousef
George M
GM
Scorilas
Andreas
A
Katsaros
Dionyssios
D
Massobrio
Marco
M
Fracchioli
Stefano
S
Diamandis
Eleftherios P
EP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D007610:Kallikreins