Differential expression of the KLK2 and KLK3 genes in peripheral blood and tissues of patients with prostate cancer

Abstract

We used the multiplex semi-quantitative reverse-transcriptase PCR (RT-PCR) to investigate kallikrein 2 and 3 (KLK2 and KLK3) mRNA levels in prostate tissue from 42 prostate cancer patients, 33 of whom were also assessed for peripheral blood KLK2 expression by qualitative semi-nested RT-PCR. We found that KLK2 was an important tissue biomarker for distinguishing between prostate cancer patients and those with benign prostatic hyperplasia, particularly when KLK2 expression was > 60% of that of the β2-microglobulin constitutive gene. Patients with an average relative expression value ≥ 0.6 (cutoff value) had an eleven-fold higher chance of having prostate cancer. When one or two tissues samples were evaluated for KLK2 expression using the cutoff value the estimated chance of having prostate cancer was increased by seven times for one positive sample and 45 times for two positive samples. There was no significant correlation between KLK3 gene expression and prostate cancer diagnosis. Logistic regression for blood and tissue KLK2 expression successfully detected 92% of the prostate cancer cases. The detection of KLK2 in blood showed a sensitivity of 59% and a specificity of 82%. This study indicates that the KLK2 gene may be a useful molecular marker for the diagnosis of prostate cancer and that analysis of KLK2 expression in blood and tissues could provide a novel approach for the clinical investigation of this type of cancer.

Gene Expression Profile of Prostate Cancer Patients by Chemiluminescent Analysis

“…These results corroborate other investigations (Bussemakers et al 1999;Volpert et al 2002;Harris et al 2003;Luo et al 2003;Neves et al 2003Neves et al , 2008, Meola et al 2006.…”

“…Several genes have been identified by their differential expression in prostate pathologies, from which 14 genes were important in prostate cancer development, such as steroid 5 alpha-reductase 2 (SRD5A2) (Luo et al 2003;Neves et al 2008), androgen receptor (AR) (Harris et al 2003;Neves et al 2003Neves et al , 2008, carcinoembryonic antigen-related cell adhesion molecule (CEACAM-1) (Volpert et al 2002), prostate cancer antigen (DD3 or PCA3) (Bussemakers et al 1999;Hessels et al 2004;Neves et al 2008), kallikrein 2 (KLK2) (Meola et al 2006;Neves et al 2008), nitric oxide synthase 3 (eNOS or NOS3) (Marangoni et al 2006), osteopontin 1 (OPN-1) (Tozawa et al 1999), tumor protein 53 (TP53) (Levine 1997), prostate-specific membrane antigen or folate hydrolase (PSMA, PSM, or FLH1) Hessels et al 2004;Neves et al 2008), prostate-specific antigen (kallikrein 3) (PSA or KLK3) (Price, Woodard, and Teigland 1995;Goulart et al 2003;Hessels et al 2004), transglutaminase P (TGP or TGM4) , prostatic carcinoma tumor-inducing gene 1=eukaryotic translation elongation factor 1A (PTI-1=EEF1A) (Gopalkrishnan, Su, and Goldstein 1999), transforming growth factor-beta 1 (TGF-b1) (Faria et al 2007), and 1,25-dihydroxyvitamin D3 receptor (VDR) .…”

A Single Glycan at the 99-Loop of Human Kallikrein-related Peptidase 2 Regulates Activation and Enzymatic Activity

“…Its activity is also regulated by several protease inhibitors, such as α 2 -antiplasmin, α 1 -antichymotrypsin, antithrombin III, α 2 -macroglobulin, and plasminogen activator inhibitor-1 ( 19 – 22 ). Recently, KLK2 has been implicated in carcinogenesis and tumor metastasis of prostate cancer ( 23 ), whereas it is a useful serum marker of prostate cancer due to its association with prostatic proliferative disorders and tissue specificity ( 24 , 25 ).…”

Differences in Gene Expression Profiles between Human Breast Tissue and Peripheral Blood Samples for Breast Cancer Detection

“…In general molecular markers will be helpful in defining risks and identifying the early stages of cancer. The search for molecular markers that can be used for the early diagnosis of breast cancer has become one of the most important objectives in clinical investigation, particularly because the current methods are invasive, show low specificity and require additional procedures for therapeutic decisions [4]. Gene expression is a common event in the progression of human cancer detection and quantification of potential tumour marker.…”