Quantitative reverse transcription-PCR assay for detection of mRNA encoding full-length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in breast cancer.
BACKGROUND
The human tissue kallikrein gene family (KLK1 to KLK15) encodes a group of 15 serine proteases (hK1 to hK15), several of which have been implicated in cancer-related processes.


METHODS
We established a specific quantitative reverse transcription-PCR assay for full-length KLK7 mRNA that excluded amplification of the exon 2 deletion splice variant (the latter does not encode a functional protease), and evaluated full-length KLK7 mRNA expression [normalized to human glucose-6-phosphate dehydrogenase (h-G6PDH)] in tumor tissue specimens from 155 breast cancer patients.


RESULTS
High KLK7 mRNA expression (continuous) was significantly associated with a better patient outcome according to both univariate (P = 0.005) and multivariate (P = 0.046) Cox survival analysis. Separation of patients by optimized dichotomization revealed a significantly better prognosis for patients with high KLK7 mRNA status (n = 89) compared with patients with low KLK7 mRNA status (n = 66) [univariate hazard ratio (HR) = 0.45 (P = 0.001); multivariate HR = 0.50 (P = 0.005)]. In the subgroup of patients not receiving adjuvant treatment (n = 69), KLK7 mRNA status was a significant prognosticator [univariate HR = 0.29 (P = 0.002); multivariate HR = 0.40 (P = 0.034)]. This subgroup was least influenced by postoperative treatment and thus best showed the impact of KLK7 expression on the natural course of breast cancer disease.


CONCLUSIONS
Expression of full-length KLK7 mRNA may represent a new prognostic marker in breast cancer disease.
Holzscheiter
Leon
L
Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
Biermann
Julia C
JC
Kotzsch
Matthias
M
Prezas
Panagiotis
P
Farthmann
Juliane
J
Baretton
Gustavo
G
Luther
Thomas
T
Tjan-Heijnen
Vivianne C G
VC
Talieri
Maroulio
M
Schmitt
Manfred
M
Sweep
Fred C G J
FC
Span
Paul N
PN
Magdolen
Viktor
V
D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C082472:KLK7 protein, human; D007610:Kallikreins