Prognostic significance of human tissue kallikrein-related peptidases 11 and 15 in gastric cancer

Abstract The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer.

Download Full-text

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer

Tumor Biology ◽

10.1007/s13277-012-0368-5 ◽

2012 ◽

Vol 33 (4) ◽

pp. 1209-1214 ◽

Cited By ~ 11

Author(s):

Constantina Petraki ◽

Youssef M. Youssef ◽

William Dubinski ◽

Zsuzsanna Lichner ◽

Andreas Scorilas ◽

...

Keyword(s):

Colorectal Cancer ◽

Human Tissue ◽

Prognostic Significance ◽

Tissue Kallikrein

Download Full-text

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer

Pathology - Research and Practice ◽

10.1016/j.prp.2011.12.010 ◽

2012 ◽

Vol 208 (2) ◽

pp. 104-108 ◽

Cited By ~ 21

Author(s):

Constantina Petraki ◽

William Dubinski ◽

Andreas Scorilas ◽

Carol Saleh ◽

Maria D. Pasic ◽

...

Keyword(s):

Colorectal Cancer ◽

Human Tissue ◽

Prognostic Significance ◽

Tissue Kallikrein

Download Full-text

Evaluation of the prognostic value of CBXs in gastric cancer patients

Scientific Reports ◽

10.1038/s41598-021-91649-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mengya He ◽

Limin Yue ◽

Haiyan Wang ◽

Feiyan Yu ◽

Mingyang Yu ◽

...

Keyword(s):

Gastric Cancer ◽

Target Genes ◽

Prognostic Significance ◽

Disease Free Survival ◽

Genetic Alterations ◽

Genetic Mutation ◽

The Cancer Genome Atlas ◽

Normal Tissues ◽

Interactive Analysis ◽

Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

Download Full-text

Kallistatin: a novel human tissue kallikrein inhibitor. Purification, characterization, and reactive center sequence.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)35690-4 ◽

1992 ◽

Vol 267 (36) ◽

pp. 25873-25880 ◽

Cited By ~ 3

Author(s):

G.X. Zhou ◽

L Chao ◽

J Chao

Keyword(s):

Human Tissue ◽

Tissue Kallikrein ◽

Kallikrein Inhibitor ◽

Reactive Center

Download Full-text

Amplification and expression of c-MET correlate with poor prognosis of patients with gastric cancer and upregulate the expression of PDL1

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab026 ◽

2021 ◽

Vol 53 (5) ◽

pp. 547-557

Author(s):

Ya’nan Yang ◽

Chenchen Wang ◽

Congqi Dai ◽

Xinyang Liu ◽

Wenhua Li ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Disease Free Survival ◽

Positive Association ◽

Her2 Positive ◽

Kaplan Meier ◽

Met Amplification ◽

Amplification Rate ◽

Cox Proportional Hazard Regression

Abstract The prognostic significance of c-MET in gastric cancer (GC) remains uncertain. In the present study, we examined the amplification, expression, and the prognostic value of c-MET, human epidermal growth factor receptor 2 (HER2), and programmed cell death 1 ligand 1 (PDL1), together with the correlations among them in a large cohort of Chinese samples. A total of 444 patients were included. The immunohistochemistry (IHC) and the dual-color silver in situ hybridization (SISH) were performed to examine their expression and amplification. Univariate and multivariate analyses were performed by the Cox proportional hazard regression model, and survival curves were estimated by the Kaplan–Meier method. The positivity determined by IHC of c-MET was 24.8%, and the MET amplification rate was 2.3%. The positivity rates of HER2 and PDL1 were 8% and 34.7%, respectively. PDL1 expression had a significantly positive association with c-MET expression. c-MET positivity played a significant prognostic role in disease-free survival (DFS) (P = 0.032). Patients with mesenchymal-epithelial transition (MET) amplification had significantly poorer prognosis on both DFS and overall survival (OS). Subgroup analysis showed that in HER2-negative patients, but not in HER2-positive patients, MET-positive patients had significantly worse DFS (P = 0.000) and OS (P = 0.006). c-MET regulated the expression of PDL1 through an AKT-dependent pathway. c-MET inhibitor enhanced the T-cell killing ability and increased the efficacy of PD1 antibody. c-MET was found to be an independent prognostic factor for DFS of GC patients. A combination of c-MET inhibitors and PD1 antibodies could enhance the killing capacity of T cells, providing a preliminary basis for the clinical research on the same combination in GC treatment.

Download Full-text

P0141 Prognostic significance of neutrophil lymphocyte ratio in patients with non-metastatic gastric cancer

European Journal of Cancer ◽

10.1016/j.ejca.2014.03.185 ◽

2014 ◽

Vol 50 ◽

pp. e49

Author(s):

R. Eghdam Zamiri ◽

M. Moghimi ◽

A. Yaghoobi Gooybari ◽

S. Keyhanian ◽

S. Mazloomzadeh ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Significance ◽

Metastatic Gastric Cancer ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

Download Full-text

Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer

Thrombosis and Haemostasis ◽

10.1160/th08-07-0471 ◽

2009 ◽

Vol 101 (04) ◽

pp. 741-747 ◽

Cited By ~ 26

Author(s):

Konstantina Mathioudaki ◽

Panagiotis Prezas ◽

Dimitra Alexopoulou ◽

Eleftherios Diamandis ◽

Dimitris Xynopoulos ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Stratum Corneum ◽

Human Tissue ◽

Serine Proteases ◽

Human Cancer ◽

Disease Free Survival ◽

Normal Colonic Mucosa ◽

Tissue Kallikrein ◽

Human Cancer Cell Lines

SummaryHuman tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.

Download Full-text