Objectives: As kallikrein-related peptidase 12 (KLK12) has been implicated in the cancer progression and alternative splicing plays significant role in this disease, the aim of this study was to examine the expression profile and the clinical impact of the KLK12 splice variants in breast cancer.

Design And Methods: Total RNA was isolated and reverse transcripted from 141 tissues. Afterwards, quantitative real-time PCR were conducted, followed by the performance of the comparative CT (2-ΔΔCT) method for relative quantification, whilst their correlation with the clinicopathological features of breast malignancies were assessed by statistical analysis.

Results: Both KLK12sv1/2 and KLK12sv3 showed higher expression in non-cancerous than in cancerous samples. KLKsv1/2 (P = 0.001) upregulated and KLK12sv3 (P < 0.001) downregulated in the malignant compared to the benign tumors and their discriminative ability was verified by ROC curve analysis. Moreover, KLK12sv3 was associated with grade (P = 0.012) and hormonal receptor status (P = 0.001). Furthermore, Kaplan-Meier and Cox regression analyses showed that patients with positive KLK12sv1/2 and KLK12sv3 levels presented a significantly longer disease-free survival (P = 0.014 and P = 0.013, respectively) and overall survival (P = 0.062 and P = 0.004, respectively).

Conclusions: Our results demonstrate the discriminative value of KLK12sv1/2 and KLK12sv3 between benign and malignant breast tumors as well as their potential favorable prognostic significance in breast adenocarcinoma.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2018.05.017DOI Listing

Publication Analysis

Top Keywords

kallikrein-related peptidase
8
peptidase klk12
8
klk12 splice
8
splice variants
8
human kallikrein-related
4
variants discriminate
4
discriminate benign
4
benign cancerous
4
cancerous breast
4
breast tumors
4

Similar Publications

Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates.

Biol Chem

December 2024

Departments of Biological Chemistry and Early Discovery Biochemistry, Genentech Inc., South San Francisco, CA, 94080, USA.

Kallikrein-related peptidase 7 (KLK7) is one of 15 members of the tissue kallikrein family and is primarily expressed in the skin epidermis. The activity of KLK7 is tightly regulated by multiple stages of maturation and reversible inhibition, similar to several other extracellular proteases. In this work, we used protease-specific inhibitors and active site variants to show that KLK7 undergoes autolysis at two separate sites in the 170 and 99 loops (chymotrypsinogen numbering), resulting in a loss of enzymatic activity.

View Article and Find Full Text PDF

The potential immunotherapy effect of Ginkgolide B thwarts oral squamous cell carcinoma progression by targeting the SREBP1/KLK8/CCL22 axis.

Phytomedicine

January 2025

Department of Molecular Biology and Cell Research, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan; Department of Hematology‑Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan.

Background: Oral cancer is a malignant tumor of the oral cavity, with regulatory T cell (Treg) infiltration associated with poor prognosis. Ginkgolide B (GB) has demonstrated effects on lipid metabolism; however, its potential immunotherapeutic effects on oral cancer have not been elaborated.

Purpose: This study aimed to explore the immunotherapeutic effects of Ginkgolide B (GB) in oral cancer.

View Article and Find Full Text PDF
Article Synopsis
  • - The study aimed to evaluate how the serine protease KLK6 affects colorectal cancer development in mice with a mutant tumor suppressor gene, finding that KLK6 expression increases significantly in tumors compared to normal tissue.
  • - Techniques like immunohistochemistry confirmed KLK6 presence, and genetically altered mice lacking KLK6 showed smaller tumor sizes and fewer adenomas, indicating KLK6's crucial role in tumor growth.
  • - The research highlights KLK6 as an important factor for intestinal tumorigenesis, suggesting it could be useful for early diagnosis of colorectal cancer.
View Article and Find Full Text PDF

Remodeling of the extracellular matrix by serine proteases as a prerequisite for cancer initiation and progression.

Matrix Biol

December 2024

Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address:

The extracellular matrix (ECM) serves as a physical scaffold for tissues that is composed of structural proteins such as laminins, collagens, proteoglycans and fibronectin, forming a three dimensional network, and a wide variety of other matrix proteins with ECM-remodeling and signaling functions. The activity of ECM-associated signaling proteins is tightly regulated. Thus, the ECM serves as a reservoir for water and growth regulatory signals.

View Article and Find Full Text PDF

Introduction: Human kallikrein-related peptidases (KLKs) represent a subgroup of 15 serine endopeptidases involved in various physiological processes and pathologies, including cancer.

Areas Covered: This review aims to provide a comprehensive overview of the KLK family, highlighting their genomic structure, expression profiles and substrate specificity. We explore the role of KLKs in tumorigenesis, emphasizing their potential as biomarkers and therapeutic targets in cancer treatment.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!