Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues.
BACKGROUND
Many members of the human kallikrein gene family are differentially expressed in cancer and a few have potential as diagnostic/prognostic markers. KLK14 is a newly discovered human kallikrein gene that is mainly expressed in the central nervous system and endocrine tissues. Since KLK14 was found to be regulated by steroid hormones in prostate cancer cell lines, we hypothesized that it will be differentially expressed in prostate cancer tissues compared to their normal counterparts.


METHODS
Matched prostate tissue samples from the cancerous and non-cancerous parts of the same prostates were obtained from 100 patients who underwent radical prostatectomy. Quantitative analysis of KLK14 expression levels were performed by real-time RT-PCR using SYBR Green I dye on the LightCycler trade mark system. Associations with clinico-pathological parameters were analyzed.


RESULTS
KLK14 overexpression in the cancerous compared to non-cancerous tissue was found in 74% of patients (P < 0.001). Mean level of expression was 154 arbitrary units (Au) in cancerous tissues and 14.2 Au in the non-cancerous tissues. The ratio of the cancerous to non-cancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P = 0.002), and in grade 3 compared to grade 1/2 tumors (P = 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score = 6 tumors (P = 0.027). No correlation was found between KLK14 tissue expression levels and serum prostate-specific antigen.


CONCLUSIONS
KLK14 expression is significantly higher in cancerous compared to non-cancerous prostatic tissue. The up-regulation of the KLK14 gene in advanced and more aggressive tumors may indicate a possible role for the hK14 protein in tumor spread and opens the possibility of hK14 being a candidate new marker for prostate cancer diagnosis and prognosis.
Yousef
George M
GM
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
Stephan
Carsten
C
Scorilas
Andreas
A
Ellatif
Mohamed Abd
MA
Jung
Klaus
K
Kristiansen
Glen
G
Jung
Monika
M
Polymeris
Mary-Ellen
ME
Diamandis
Eleftherios P
EP
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C425336:KLK14 protein, human; D007610:Kallikreins