Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer.
To study KLK14 gene expression in endocrine-related cancers, we studied its hormonal regulation in breast and ovarian cancer cell lines. Our kinetic and blocking experiments suggest that this up-regulation is mediated through the androgen receptor. We then studied the expression of KLK14 by quantitative reverse transcriptase-polymerase chain reaction in 155 consecutive ovarian tumors and correlated these findings with clinicopathologic parameters, response to chemotherapy, and survival. A stepwise reduction was observed in the levels of KLK14 messenger RNA in normal, benign, and cancerous tissues (P < .001). Expression levels were significantly higher in patients with early stage disease and optimal debulking and in patients who responded to chemotherapy. Kaplan-Meier survival curves demonstrated longer progression-free and overall survival in patients with KLK14-positive tumors than in patients with KLK14-negative tumors (P < .001). When all other prognostic variables were controlled in the multivariate analysis, KLK14 retained its prognostic significance (progression-free and overall survival, respectively, hazard ratios, 0.43 and 0.53; P = .027 and .014). A weak negative correlation was found between KLK14 expression and serum CA-125. KLK14 is a new, independent, and favorable prognostic marker for ovarian cancer.
Yousef
George M
GM
Dept of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Ontario, Canada M5G 1X5.
Fracchioli
Stefano
S
Scorilas
Andreas
A
Borgoño
Carla A
CA
Iskander
Lisa
L
Puopolo
Manuela
M
Massobrio
Marco
M
Diamandis
Eleftherios P
EP
Katsaros
Dionyssios
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011944:Receptors, Androgen; D013256:Steroids; C425336:KLK14 protein, human; D007610:Kallikreins