Therefore, a panel of molecular prognostic biomarkers that have recently emerged--e.g., the human leukocyte antigen (HLA-G) [56], high histone deacetylase (HDAC) activity [57], mRNA expression of kallikrein-related peptidase 14 (KLK14) [58] and BCL2-like 12 (BCL2L12) [59], circulating miR-150 [60], SRY-box 1 (SOX1) [61], and serum soluble transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) [62]--could prove even more promising, provided that it integrates miR-155-5p expression as a new component.
Scorilas, "mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients," Clinical Chemistry and Laboratory Medicine, vol.
Among these KLKs, corneocyte desquamation is mainly conducted by KLK5, KLK7, and KLK14 [47].
Additionally, KLK5 and KLK14 activate proteinase-activated receptor- (PAR-) 2, which is a G-protein-coupled receptor expressed on KCs, leading to the elicitation of itch common with AD [58].
On the other hand, results obtained with exome chips (ftp://share.sph.umich.edu/exomeChip/Proposed Content/codingContent) have indicated the occurrence of stop codons in several KLK genes, including KLK4, KLK9, KLK10, and KLK14. That would be consistent with fewer functional constraints in this cluster, which would increase the frequency of gene inactivations compared with other genomic regions.
[8] Human genes: KLK3, kallikrein-related peptidase 3; TERT, telomerase reverse transcriptase; FGFR2, fibroblast growth factor receptor 2; TBBX3, T-box protein 3; KLK15, kallikrein-related peptidase 15; KLK2, kallikrein-related peptidase 2; KLK1, kallikrein-related peptidase 1; ACPT, acid phosphatase, testicular; GPR32, G protein-coupled receptor 32; INS, insulin; KLK4, kallikrein-related peptidase 4; KLK9, kallikrein-related peptidase 9; KLK10, kallikrein-related peptidase 10; KLK14, kallikrein-related peptidase 14.
KLK11, KLK13, and KLK14 were measured as previously described (18, 19) (see Supplemental Data section in the online Data Supplement).
The KLK8 mRNAs were considered alone or as a ratio with the KLK5, KLK6, KLK7, KLK10, KLK11, KLK13, or KLK14 mRNA in the same samples.
Highest concentrations of
KLK14 were found in fetal skin and cartilage.
Previously, several other kallikreins, including KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11,
KLK14, and KLK15, have been associated with various forms of malignancy and especially cancers of the ovary, breast, prostate, and testis [reviewed in Refs.
Telomeric to the last kallikrein gene,
KLK14, lies another nonkallikrein gene, Siglec 9, a member of the Siglec multigene family (9,10).
It is possible that in the future, new members of this gene family may be identified, either centromeric to KLK1 or telomeric to
KLK14. If new kallikrein genes are identified in this locus, they will be numbered sequentially, starting with KLK15.