Kallikrein-related peptidase 6 (KLK6)gene expression in intracranial tumors

Kallikrein-related peptidases (KLKs) are emerging novel new biomarkers for prognosis, diagnosis and therapeutic intervention of cancer. Kallikrein-related peptidase 6 (KLK6) has the highest expression in normal brain among other tissues. Although its expression has been extensively studied in many types of cancer and in neurodegenerative diseases, very little is known for its expression in intracranial tumors. In the present study, 73 intracranial tumor samples were examined for KLK6 messenger ribunucleic acid (mRNA) gene expression using quantitative real-time polymerase chain reaction. Statistical analysis revealed the significant association of KLK6 expression with clinical and pathological parameters. Follow-up information was available for a median time of 20 months (range 1-59 months). KLK6 is expressed more frequently in tumors of high malignancy like the glioblastomas (70.6 %) and less in tumors of low malignancy like the meningiomas (12.5 %). KLK6 positive expression is associated with tumor grade (p < 0.001), malignancy status (p < 0.001), and tumor histologic type (p = 0.001). Cox proportional hazard regression model using univariate analysis revealed for the first time that positive KLK6 expression is a significant factor for disease-free survival (DFS; p = 0.041) of patients suffering from intracranial tumors. Kaplan-Meier survival curves demonstrated that negative KLK6 expression is significantly associated with longer DFS (p = 0.032). KLK6 gene expression may have clinical utility as a marker of unfavorable prognosis for intracranial tumors, and consequently, it could be used as target for therapeutic intervention. © 2012 International Society of Oncology and BioMarkers (ISOBM)

Parallel overexpression and clinical significance of kallikrein-related peptidases 7 and 14 (KLK7 & KLK14) in colon cancer

Currently available colon cancer (CC) markers lack sensitivity and specificity. Kallikrein-related peptidases (KLKs) present a new class of biomarkers under investigation for diverse diseases, including cancer. KLKs are co-expressed in various tissues participating in proteolytic cascades. KLK7 in human tumours facilitates metastasis by degrading components of the extracellular matrix. KLK14 promotes tumourigenesis by activating proteinase-activated receptors. In the present study we examined the concomitant expression of KLK7 and KLK14 in 245 colonic tissue specimens from 175 patients; 70 were pairs of cancerous- normal tissues, 31 were cancerous tissues and 74 were colonic adenomas. We used quantitative real-time PCR and proved that both genes are up-regulated in CC at the mRNA level. Receiver-operating characteristic (ROC) analysis of our results showed that both genes have discriminatory value between CC and adenoma tissues, with KLK14 obtaining greater distinguishing power (area under the curve [AUC]=0.708 for KLK14; AUC=0.669 for KLK7). Current work showed that the two genes are fairly co-expressed in all three types of colon tissues examined (normal rs=0.667, p<0.001, adenomas rs=0.373, p=0.001, carcinomas rs=0.478, p<0.001). KLK14 is associated with shorter disease-free survival (DFS) and overall survival (OS) of patients (p=0.003, p=0.016 respectively), whereas KLK7 only with shorter DFS (p=0.004). KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for CC patients with discriminating power between CC and adenoma patients. © Schattauer 2013

Cathepsin B protein levels in endometrial cancer: Potential value as a tumour biomarker

Objective: Lysosomal cysteine protease Cathepsin-B has been implicated in the progression of various human tumours. We examined Cathepsin-B protein levels in endometrial carcinoma patients-mainly post-menopausal-and investigated their possible association with clinical and pathological parameters in order to assess Cathepsin-B's significance as a potential tumour biomarker. Methods: The indirect immunoperoxidase method was used for Cathepsin-B immunohistochemical staining of 64 paraffin-embedded endometrial tumour tissues, having follow-up period of 18-240 months. Steroid hormone receptors were measured as well. Tissue samples were staged following the FIGO criteria. Results: Positive Cathepsin-B immunostaining was observed in 27 patients (42.2%) and was significantly associated with the FIGO stage of the disease (p = 0.006), as well as cervical and stromal invasion (p = 0.001 and p = 0.037, respectively) and progesterone receptor status (p = 0.027). Positive Cathepsin-B expression was also inversely related to Disease-free Survival (p = 0.034) and Overall Survival (p = 0.035) in univariate analysis, as well as in multivariate analysis (p = 0.022 and p = 0.035, respectively). Conclusion: Increased Cathepsin-B expression was found to be predictive of more aggressive tumour behaviour over time and can be regarded as an unfavourable and independent tumour marker for endometrial cancer patients with a long follow-up. © 2008 Elsevier Inc

Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence

Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases located on chromosome 19q13.3. Most KLKs have been extensively studied as potential biomarkers for several carcinomas and other diseases. KLK5 was originally identified from a keratinocyte library, and its enzyme was purified from the stratum corneum of human skin. KLK5 was shown to be differentially expressed in a variety of endocrine tumors, although it is not as yet examined widely in colorectal cancer (CRC). In this study, we quantitatively assessed the mRNA expression status of KLK5 in 197 colorectal tissues from 133 patients (70 cancerous and their paired normal colonic mucosa for 64 of them, as well as 63 colorectal adenomas) by quantitative real-time PCR (qPCR) using TaqMan probes. Statistical analysis evaluated the results. It was shown that KLK5 expression is reduced following the histologically non-cancerous-adenoma sequence (p<0.001), whereas it is increased during the sequence adenoma-carcinoma (p<0.001). Furthermore, KLK5 positive expression is associated with positive nodal status (p=0.022), advanced tumor stage (p=0.038) and high histological grade (p=0.033). Cox univariate analysis revealed that KLK5 positive expression is associated with disease-free survival (DFS) (p=0.028) and overall survival (OS) of patients (p=0.048). Kaplan-Meyer survival models showed that patients with positive KLK5 expression have lower DFS (p=0.009) and OS (p=0.019). Receiver operating characteristic (ROC) analysis demonstrated for first time that KLK5 expression had significant discriminatory values between cancer and adenoma tissues (area under the curve [AUC] 0.77; 95% confidence interval [CI]=0.69-0.85, p=0.03). KLK5 mRNA expression may be useful for the differentiation of CRC from colorectal adenoma and represents a potential unfavorable prognostic biomarker for CRC. © 2019 Walter de Gruyter GmbH, Berlin/Boston

Clinical evaluation of PRMT1 gene expression in breast cancer

Methylation of arginine residues has been implicated in many cellular activities like mRNA splicing, transcription regulation, signal transduction and protein- protein interactions. Protein arginine methyltransferases are the enzymes responsible for this modification in living cells. The most commonly used methyltransferase in man is protein arginine methyltransferase 1 (PRMT1). Since methylation processes appear to interfere in the emergence of several diseases, including cancer, we investigated the localisation of the protein in cancer tissue and, for the first time, the relation that possibly exists between the expression of PRMT1 gene and breast cancer progression. We used tumour specimens from 62 breast cancer patients and semi-quantitative RT-PCR to determine the expression of PRMT1 gene and was found to be associated with patient's age (p=0.002), menopausal status (p=0.006), tumour grade (p=0.03), and progesterone receptor status (p=0.001). Survival curves revealed that PRMT1-v1 status-low expression relates to longer disease-free survival (DFS; p=0.036). To the contrary, PRMT1-v2 status is not associated neither with the clinical or pathological parameters nor with DFS (p=0.31). PRMT1-v3 was not statistically significantly expressed in breast cancer tissue. Selected cancer and normal breast samples were stained for PRMT1. In both normal and cancerous breast tissues, staining was in the cytoplasm and only in rare cases the cell nucleus appeared stained. Present results show a potential use for this gene as a marker of unfavourable prognosis for breast cancer patients. © 2010 International Society of Oncology and BioMarkers (ISOBM)

Expression analysis and clinical evaluation of kallikrein-related peptidase 10 (KLK10) in colorectal cancer

Kallikrein-related peptidases (KLKs) represent a serine protease family having 15 members. KLK10 is a secreted protease with a trypsin-like activity. The function of KLK10 is poorly understood, although it has been suggested that KLK10 may function as a tumor suppressor gene. In human cancer, KLK10 gene shows organ-specific up- or down-regulation. Since KLKs are promising tumor biomarkers, the examination of KLK10 mRNA expression and its association with colorectal cancer (CRC) progression was studied using semi-quantitative PCR. One hundred and nineteen primary CRC specimens were examined for which follow-up information was available for a median period of 29 months (range, 1-104 months). KLK10 expression was found to be significantly associated with TNM stage (p=0.028). Cox proportional hazard regression model using univariate analysis revealed for the first time that high status KLK10 expression is a significant factor for disease-free survival (DFS; p= 0.002) and overall survival (OS; p=0.026) of patients. Kaplan-Meier survival curves demonstrated that KLK10 expression of low status is significantly associated with longer DFS (p=0.001) as well as OS (p=0.021), suggesting that KLK10 gene expression may be used as a marker of unfavorable prognosis for CRC. As the epigenetics of cancer are unraveled, KLK10 may represent not only a novel biomarker, but also a promising future therapeutic target for the disease. © International Society of Oncology and BioMarkers (ISOBM) 2011