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LMTK2作为临床意义不显著和临床意义显著的前列腺癌分层的潜在生物标志物。

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

作者信息

Vezelis Alvydas, Simiene Julija, Dabkeviciene Daiva, Kincius Marius, Ulys Albertas, Suziedelis Kestutis, Jarmalaite Sonata, Jankevicius Feliksas

机构信息

National Cancer Institute, Santariskiu Street 1, Vilnius, LT 08660, Lithuania.

Life Sciences Center, Vilnius University, Sauletekio Ave., 7, Vilnius, LT 08412, Lithuania.

出版信息

J Oncol. 2021 Jan 5;2021:8820366. doi: 10.1155/2021/8820366. eCollection 2021.

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 ( = 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.

摘要

一组前列腺肿瘤往往生长缓慢,不需要积极治疗。因此,区分具有临床意义和无临床意义的前列腺癌(PC)患者仍然是避免过度治疗的关键问题。基因技术的快速发展加速了用于可靠PC诊断的下一代分子工具的开发。本研究的目的是评估分子生物标志物(CRISP3、LMTK2和MSMB)在区分PC病例与良性前列腺病变方面的诊断价值,更具体地说,是在PSA水平升高的患者中,从所有PC病例中识别出具有临床意义的PC。因PSA升高(PSA I)经直肠系统前列腺活检阴性后PSA升高(PSA II)的患者(n = 200)符合本研究条件。除了PSA浓度外,还计算了每位患者的PSA密度。应用RT-PCR检测病例外周血样本中的基因表达水平,同时通过焦磷酸测序鉴定MSMB(-57 C/T)多态性。LMTK2和MSMB显著区分对照组与BPD组和PC组。MSMB表达倾向于从CC基因型的主要等位基因向TT基因型的次要等位基因增加。PSA密度是唯一能显著区分具有临床意义的PC和无临床意义的PC的临床特征。因此,LMTK2表达和PSA密度在具有临床意义的PC和无临床意义的PC之间有显著差异。PSA密度而非PSA能区分PC与良性前列腺疾病,并且与LMTK2结合,有助于区分无临床意义和有临床意义的PC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2305/7803409/5729f5021340/JO2021-8820366.001.jpg

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