LMTK2 as Potential Biomarker for Stratification between Clinically Insignificant and Clinically Significant Prostate Cancer

Abstract

A set of prostate tumors tend to grow slowly and do not require active treatment. Therefore, stratification between patients with clinically significant and clinically insignificant prostate cancer (PC) remains a vital issue to avoid overtreatment. Fast development of genetic technologies accelerated development of next-generation molecular tools for reliable PC diagnosis. The aim of this study is to evaluate the diagnostic value of molecular biomarkers (CRISP3, LMTK2, and MSMB) for separation of PC cases from benign prostatic changes and more specifically for identification of clinically significant PC from all pool of PC cases in patients with rising PSA levels. Patients (n = 200) who had rising PSA (PSA II) after negative transrectal systematic prostate biopsy due to elevated PSA (PSA I) were eligible to the study. In addition to PSA concentration, PSA density was calculated for each patient. Gene expression level was measured in peripheral blood samples of cases applying RT-PCR, while MSMB (−57 C/T) polymorphism was identified by pyrosequencing. LMTK2 and MSMB significantly differentiated control group from both BPD and PC groups. MSMB expression tended to increase from the major alleles of the CC genotype to the minor alleles of the TT genotype. PSA density was the only clinical characteristic that significantly differentiated clinically significant PC from clinically insignificant PC. Therefore, LMTK2 expression and PSA density were significantly distinguished between clinically significant PC and clinically insignificant PC. PSA density rather than PSA can differentiate PC from the benign prostate disease and, in combination with LMTK2, assist in stratification between clinically insignificant and clinically significant PC.

Lemur Tyrosine Kinases and Prostate Cancer: A Literature Review

“…Their level of expression appears to be reduced in human prostate tissue as compared to normal tissue [ 57 , 60 , 68 ]. Additionally, LMTK2 blood level has been shown to contribute to the identification of clinically significant PCa [ 61 ]. We report that both LMTK2 and LMTK3 interact with, and modulate, the activity of specific enzymes of the signalling cascades regulating cell growth, differentiation, and apoptosis in PCa cells.…”

“…The publication date range considered for study selection was January 2005–January 2020, although a literature search performed in March 2021 added a supplemental study [ 61 ].…”

“…Gene expression analysis was used to investigate the potential association of LMTK2 with the development of PCa in two different studies [ 60 , 61 ] ( Table 2 ). The first study evaluated the expression of 7 PCa candidate genes in cancer versus benign prostatic hyperplasia (BPH) samples, in correlation with genotype at risk variants identified by genome-wide association studies (GWAS) [ 60 ].…”

“…The data confirm that the risk genotype at the GWAS variant rs6465657 correlates with LMTK2 expression and that prostate adenocarcinoma samples expresses 68% less LMTK2 mRNA than BPH samples, providing strong evidence for the role of this gene in PCa progression. The second study examined the expression level of LMTK2 in blood samples of prostate cancer patients, with the aim of making use of LMTK2 level as a potential biomarker for stratification between clinically insignificant and clinically significant PCa patients [ 61 ]. LMTK2 expression significantly decreases in blood samples of patients with PCa versus BPH as compared to control (with high PSA but no PCa), while PSA density value (ng/mL, based on PSA measurement divided by prostate volume) can differentiate PCa from benign prostate disease.…”

“…Gene expression analysis was used to investigate the potential association of LMTK2 with the development of PCa in two different studies [60,61] (Table 2). The first study…”