Expression of human Kallikrein 14 (KLK14) in breast cancer (original) (raw)
Related papers
British Journal of Cancer, 2002
KLK14 (formerly known as KLK-L6) is a recently identified member of the human kallikrein gene family. This family harbours several genes aberrantly expressed in various cancers as well as established (PSA/hK3, hK2) and potential (hK6, hK10) cancer markers. Similar to other kallikrein genes, KLK14 was found to be regulated by steroid hormones, particularly androgens and progestins, in breast and ovarian cancer cell lines. Preliminary studies indicated that KLK14 is differentially expressed in breast, ovarian, prostatic and testicular tumours. Given the above, we determined the prognostic significance of KLK14 expression in breast cancer. We studied KLK14 expression in 178 histologically confirmed epithelial breast carcinomas by quantitative reverse transcription-polymerase chain reaction and correlated with clinicopathological variables (tumour stage, grade, histotype etc.) and with outcome (disease-free survival and overall survival), monitored over a median of 76 months. KLK14 mRNA levels ranged from 0 to 1219 arbitrary units in breast cancer tissues, with a mean+s.e. of 136+22. An optimal cutoff value of 40.5 arbitrary units was selected, to categorise tumours as KLK14-positive or negative. Higher concentrations of KLK14 mRNA were more frequently found in patients with advanced stage (III) disease (P=0.032). No statistically significant association was found between KLK14 and the other clinicopathological variables. KLK14 overexpression was found to be a significant predictor of decreased disease-free survival (hazard ratio of 2.31, P=0.001) and overall survival (hazard ratio of 2.21, P=0.005). Cox multivariate analysis indicated that KLK14 was an independent prognostic indicator of disease-free survival and overall survival. KLK14 also has independent prognostic value in subgroups of patients with a tumour size 42 cm and positive nodal, oestrogen receptor and progestin receptor status. We conclude that KLK14 expression, as assessed by quantitative reverse transcription-polymerase chain reaction, is an independent marker of unfavourable prognosis for breast cancer.
British Journal of Cancer, 2002
Kallikreins are a group of serine proteases with diverse physiological functions. KLK13 (previously known as KLK-L4) is a novel kallikrein gene located on chromosome 19q13.4 and shares a high degree of homology with other kallikrein family members. Many kallikrein genes were found to be differentially expressed in various malignancies, and their regulation is controlled by steroid hormones in prostate and breast cancer cell lines. We studied the expression of KLK13 by quantitative reverse transcriptase-polymerase chain reaction in 173 patients with epithelial breast carcinoma. An optimal cutoff point equal to the 40th percentile was defined, based on the ability of KLK13 to predict disease-free survival. KLK13 values were then associated with other established prognostic factors and with disease-free survival and overall survival. Higher positivity for KLK13 expression was found in older, oestrogen receptor positive patients. In univariate analysis, KLK13 expression is a significant predictor of improved disease-free survival and overall survival (P50.001 and P=0.009, respectively). Cox multivariate analysis indicated that KLK13 was an independent prognostic variable in the subgroups of patients with Grade I-II tumours and in patients who were oestrogen receptor and progesterone receptor positive, and node positive. Hazard ratios derived from Cox analysis, related to disease-free survival and overall survival were 0.22 (P=0.001) and 0.24 (P=0.008), respectively, for the Grade I-II group; 0.36 (P=0.008) and 0.44 (P=0.038), respectively, for the node positive group and 0.36 (P=0.008) and 0.18 (P=0.008), respectively, for the oestrogen receptor positive group. The adjusted hazard ratio for progesterone receptor positive patients for disease-free survival was 0.25 (P=0.012). For patients in the node positive and oestrogen receptor positive subgroup (n=51) the adjusted hazard ratio was 0.25 (P=0.006) and for the node positive and progesterone receptor positive subgroup (n=46) the hazard ratio was 0.24 (P=0.008). Taken together, these data suggest that higher KLK13 expression in these subgroups of breast cancer patients is associated with an approximately 55 to 80% reduction in the risk of relapse or death. We conclude that KLK13 expression, as assessed by quantitative reverse transcriptase-polymerase chain reaction, is an independent favourable prognostic marker for breast carcinoma.
Expression analysis and study of KLK4 in benign and malignant breast tumours
Thrombosis and Haemostasis, 2009
SummaryThe steroid hormone-regulated gene KLK4 (kallikrein 4) is a new member of the human kallikrein-related peptidase gene family. Up to date, studies report that KLK4 is differentially expressed in many tumours. The purpose of this study was the expression analysis and study of KLK4 in benign and malignant breast tumours. Total RNA was isolated from 16 benign and 45 malignant breast tissue specimens. After testing RNA quality, cDNA was prepared by reverse transcription. Highly sensitive quantitative real-time PCR method for KLK4 mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method 2-ΔΔCT. KLK4 expression was found to vary in both patients’ cohorts; however, a statistically significant elevation of the KLK4 mRNA levels was observed in malignant compared to benign tumour patients. Low KLK4 expression levels were found in well-differentiated tumours (p=0.0...
Thrombosis and Haemostasis, 2003
Kallikreins are a subgroup of serine proteases that are involved in the post-translational processing of polypeptide precursors. Growing evidence suggests that many kallikreins are implicated in carcinogenesis. Human kallikrein gene 7 (KLK7; HSCCE) is a new member of the human kallikrein gene family. KLK7 is expressed in normal breast tissue and is up-regulated in breast cancer cells by estrogens and glucocorticoids. In the present study, expression of the KLK7 gene in 92 breast cancer tissues was analyzed by reverse transcription-PCR (RT-PCR) and direct sequencing of several samples. The results were correlated with other clinicopathological variables and patient outcome. KLK7 gene expression was significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and patients with positive progesterone receptors (p = 0.022). Survival analysis showed that breast cancer patients with KLK7 positive tumors have relatively shorter disease-free survival (DFS) and overall survival (OS) than patients with KLK7 negative tumors. These data suggest that KLK7 gene expression may be used as a marker of unfavorable prognosis for breast cancer patients.
British Journal of Cancer, 2002
Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 is newly discovered kallikrein gene that is located adjacent to KLK3 on chromosome 19q13.4. KLK15 has 41% similarity to KLK3 and the encoded protein, hK15, can activate proprostate specific antigen. We studied the expression of KLK15 by real-time quantitative reverse transcriptase -polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types. KLK15 expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and P=0.011) and overall survival (hazard ratio of 0.34 and P=0.009). When all other known confounders were controlled in the multivariate analysis, KLK15 retained its prognostic significance. Higher concentrations of KLK15 mRNA were found more frequently in node negative patients (P=0.042). No association was found between KLK15 expression and any other clinicopathological variable. Further, KLK15 is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis. KLK15 levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients. KLK15 is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor.
Clinical Chemistry, 2006
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 h...
Kallikrein 11 Down-regulation in Breast Carcinoma: Correlation With Prognostic Parameters
In Vivo, 2021
Background: Expression of kallikrein-11 (KLK11) has been found to be related to the prognosis of various human cancer types but its physiological functions in the steps of breast cancer (BC) progression are still unknown. Materials and Methods: BC and adjacent normal breast tissue samples were collected from 28 patients. KLK11 expression levels were determined by real-time polymerase chain reaction for each sample and associations with known prognostic features were statistically analyzed. Results: Although there was slight up-regulation in tumor tissues overall, significant down-regulation of KLK11 expression in tumor tissue was observed in the elderly and in patients with perineural invasion. Furthermore, tumor size, grade, mitotic score, necrosis, calcification, lymphatic invasion, hormone receptor status and Ki67 expression were associated with altered KLK11 level. Conclusion: Changes in expression levels of KLK11, associated with patient characteristics, might be used as complementary data in order to predict clinical outcome and prognosis in BC.
The Prostate, 2003
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 TM 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 noncancerous KLK14 expression values was higher in patients with late stage (stage III) compared to stage II (P ¼ 0.002), and in grade 3 compared to grade 1/2 tumors (P ¼ 0.001). A statistically significant increase was also observed in patients with higher in Gleason score (>6) compared to Gleason score ¼ 6 tumors (P ¼ 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 noncancerous 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.
Human Kallikrein 13 Protein in Ovarian Cancer Cytosols: A New Favorable Prognostic Marker
Journal of Clinical Oncology, 2004
PurposeHuman kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.Patients and MethodsUsing a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 ovarian tumor extracts and correlated with various clinicopathological variables and outcome (progression-free survival [PFS], overall survival [OS]), over a median follow-up period of 42 months.ResultshK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67thpercentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to cate...