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

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.

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Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer

Biological Chemistry ◽

10.1515/hsz-2014-0143 ◽

2014 ◽

Vol 395 (9) ◽

pp. 1087-1093 ◽

Cited By ~ 14

Author(s):

David L. Kolin ◽

Keiyan Sy ◽

Fabio Rotondo ◽

Mena N. Bassily ◽

Kalman Kovacs ◽

...

Keyword(s):

Gastric Cancer ◽

Tissue Microarray ◽

Human Tissue ◽

Serine Proteases ◽

Prognostic Significance ◽

Staining Intensity ◽

Clinicopathological Parameters ◽

Tissue Kallikrein ◽

Advanced Stage ◽

Stage Disease

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.

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

Tumor Biology ◽

10.1007/s13277-015-3802-7 ◽

2015 ◽

Vol 37 (1) ◽

pp. 437-446 ◽

Cited By ~ 5

Author(s):

David L. Kolin ◽

Keiyan Sy ◽

Fabio Rotondo ◽

Mena N. Bassily ◽

Kalman Kovacs ◽

...

Keyword(s):

Gastric Cancer ◽

Human Tissue ◽

Prognostic Significance ◽

Tissue Kallikrein

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Faculty Opinions recommendation of Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1163368.625084 ◽

2009 ◽

Author(s):

Pedro Romero ◽

Jean-Paul Rivals ◽

Camilla Jandus

Keyword(s):

Colorectal Cancer ◽

T Regulatory Cells ◽

Prognostic Significance ◽

Regulatory Cells

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Faculty Opinions recommendation of Prognostic significance of lymphovascular invasion in sporadic colorectal cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3403956.3098054 ◽

2010 ◽

Author(s):

Heidi K Chua

Keyword(s):

Colorectal Cancer ◽

Lymphovascular Invasion ◽

Prognostic Significance ◽

Sporadic Colorectal Cancer

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The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-90220-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu Zhang ◽

Zhaohui Zhong ◽

Mei Li ◽

Jingyi Chen ◽

Tingru Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

The Cancer Genome Atlas ◽

Actin Dynamics ◽

Elevated Expression ◽

Sw480 Cells ◽

And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

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Prognostic significance of bone marrow and spleen 18F-FDG uptake in patients with colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-91608-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jae-Hoon Lee ◽

Hye Sun Lee ◽

Soyoung Kim ◽

Eun Jung Park ◽

Seung Hyuk Baik ◽

...

Keyword(s):

Colorectal Cancer ◽

Bone Marrow ◽

Inflammatory Markers ◽

Univariate Analysis ◽

Prognostic Significance ◽

Uptake Ratio ◽

Liver Uptake ◽

Fdg Uptake ◽

Standardized Uptake Values ◽

Serum Inflammatory Markers

AbstractSerum inflammatory markers are used in the prognostication of colorectal cancer (CRC); however, the corresponding role of positron emission tomography (PET)-derived inflammatory markers remains unclear. This study aimed to investigate the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow and spleen of patients with CRC and evaluate the relationship between FDG uptake estimates in these organs and serum inflammatory markers. In total, 411 patients who underwent preoperative FDG PET/computed tomography (CT) within 1 month of surgery were enrolled. The mean standardized uptake values of the bone marrow and spleen were normalized to the value of the liver, thereby generating bone marrow-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) estimates. The value of BLR and SLR in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between BLR or SLR and neutrophil-to-lymphocyte ratio (NLR) was evaluated. The predictive accuracy of BLR alone and in combination with SLR was compared using the integrated area under the receiver operating characteristic curves (iAUC). In the univariate analysis, BLR (> 1.06) and SLR (> 0.93) were significant predictors of OS. In the multivariate analysis, BLR was an independent predictor of OS (hazard ratio = 5.279; p < 0.001). Both BLR and SLR were correlated with NLR (p < 0.001). A combination of BLR and SLR was better than BLR alone at CRC prognostication (iAUC, 0.561 vs. 0.542). FDG uptake estimates in the bone marrow and spleen may be useful imaging-derived biomarkers of systemic inflammation, supporting CRC prognostication.

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