ST14 gene variant and decreased matriptase protein expression predict poor breast cancer survival.
BACKGROUND
Matriptase plays a role in carcinogenesis, but the role of its genetic variation or that of the hepatocyte growth factor activator inhibitor-1 (HAI-1) has not been evaluated. This study aimed to examine the genetic variation of matriptase (ST14 gene) and HAI-1 (SPINT1 gene) in breast cancer risk and prognosis, to assess matriptase and HAI-1 gene and protein expression in breast tumors, and to identify their clinicopathologic correlations and prognostic significance.


METHODS
Five single nucleotide polymorphisms in ST14 and three in SPINT1 were genotyped in 470 invasive breast cancer cases and 446 healthy controls. Gene expression analysis was done for 40 breast cancer samples. Protein expression was assessed by immunohistochemical analyses in 377 invasive breast tumors. The statistical significance of the associations among genotypes, clinicopathologic variables, and prognosis was assessed.


RESULTS
The ST14 single nucleotide polymorphism rs704624 independently predicted breast cancer survival, a poor outcome associated with the minor allele (P = 0.001; risk ratio, 2.221; 95% confidence interval, 1.382-3.568). Moreover, ST14 gene expression levels were lower among the minor allele carriers (P = 0.009), and negative/low matriptase protein expression was independently predictive of poorer survival (P = 0.046; risk ratio, 1.554; 95% confidence interval, 1.008-2.396).


CONCLUSIONS
The ST14 variant rs704624 and protein expression of matriptase have prognostic significance in breast cancer. This study adds to the evidence for the role of matriptase in breast cancer and has found new evidence for the genotypes having an impact in breast cancer.


CONCLUSIONS
This is the first study showing that genetic variation in matriptase has clinical importance. The results encourage further study on the genetic variation affecting protein levels and function in type II transmembrane serine proteases.
Kauppinen
Jaana M
JM
Department of Pathology, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland and Kuopio University Hospital, Biocenter Kuopio, Finland. jaana.kauppinen@uef.fi
Kosma
Veli-Matti
VM
Soini
Ylermi
Y
Sironen
Reijo
R
Nissinen
Minna
M
Nykopp
Timo K
TK
Kärjä
Vesa
V
Eskelinen
Matti
M
Kataja
Vesa
V
Mannermaa
Arto
A
D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate
D053491:Proteinase Inhibitory Proteins, Secretory; C109149:SPINT1 protein, human; D012697:Serine Endopeptidases; C485596:ST14 protein, human