Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy

Abstract

PurposeThe human kallikrein-2 (hK2) protein and two single nucleotide polymorphism (SNPs) (rs2664155, rs198977) of the gene are associated with prostate cancer risk. We examined whether hK2 protein and gene SNPs predict prostate cancer at the time of repeat biopsy.MethodsWe prospectively offered a repeat biopsy to men with a negative prostate biopsy performed for a PSA >4.0 ng/mL or abnormal Digital Rectal Exam (DRE) between 2001–2005. We genotyped and measured serum hK2 levels in 941 men who underwent a repeat prostate biopsy. Logistic regression analyses were conducted to determine the significance of KLK2 SNPs and hK2 levels for predicting cancer at repeat biopsy.ResultsOf the 941 patients, 180 (19.1%) were found to have cancer. The rs198977 SNP was positively associated with cancer at repeat biopsy (OR variant T allele = 1.8, 95% CI: 1.04-3.13, p = 0.049). When combined, the odds ratio for prostate cancer for patients with high hK2 levels and the variant T-allele of rs198977 was 3.77 (95% CI: 1.94-7.32, p < 0.0001), compared to patients with low hK2 levels and the C-allele. The addition of hK2 levels and KLK2 rs198977 to the baseline predictive model did not significantly increase the area under the curve from a baseline model of 0.67 to 0.69 (p = 0.6).ConclusionsThe KLK2 SNP rs198977 was positively associated with hK2 levels and predicts prostate cancer at the time of repeat prostate biopsy. Further characterization of the KLK2 gene will be needed to determine its clinical utility.

Diagnostic performance of PCA3 and hK2 in combination with serum PSA for prostate cancer

“…Many experiments have confirmed that the serum hK2 is helpful to the detection of Pca and prognosis. [ 12 ] We found when the cut-off is 268.33, the sensitivity was 25.6% and the specificity was 96.5% of hK2, with an AUC of 0.607 (95% CI: 0.493–0.721), the results was familiar with other studies. What's more, for those patients with PSA “grey area,” the sensitivity was up to 60.0% and the specificity to 94.3%.…”

“…Human kallikrein 2 is a kind of serine protease, which possesses 79% of the amino acid sequence identical with PSA, is also a novel biomarker for Pca. [ 11 , 12 ] hK2 is mostly produced in the prostate, secreting with the form of proenzyme in the body and outside the cell is activated into active enzymes. hK2 exists in blood, semen and saliva, and other bodily fluids, furthermore, 80% to 95% of hK2 in the blood exists in the free form.…”

Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in&nbsp;castration-resistant prostate cancer

“… 34 The kallikreins KLK2 and KLK3 are a subgroup of serine proteases implicated in carcinogenesis and have potential roles as novel cancer biomarkers. 35 PSA protein is the product of the KLK3 gene used in the diagnosis and monitoring of prostate cancer. 36 SLC12A1 plays a vital role in the regulation of ionic balance and cell volume.…”

The Molecular Biology of Prostate Cancer: Diagnosis, Resistance and Virulence

“…As such, many SNPs that have been associated with prostate cancer may not even contribute to the actual aberration in function or expression that leads to prostate cancer development and morbidity [35]. Other studies have shown however that some SNPs are in fact involved in the control of expression and function of some genes such as the previously mentioned TMPRSS2 [36,37].…”