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Plasma hTERT mRNA discriminates between clinically localized and locally advanced disease and is a predictor of recurrence in prostate cancer patients

机译:血浆hTERT mRNA可以区分临床局部疾病和局部晚期疾病,是前列腺癌患者复发的预测因子

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Introduction: Since the introduction of prostate-specific antigen (PSA) testing, new prostate cancer (PCa) patients are diagnosed earlier and most have localized and locally advanced disease. Current diagnosis methods lack specificity and sensitivity, leading to overdiagnosis and overtreatment of patients with low-risk organ-confined localized disease. Therefore, new non-invasive molecular tools are needed to discriminate between localized and locally advanced disease.Methods: Plasma telomerase reverse transcriptase (hTERT) mRNA levels were determined by qRT-PCR in 49 patients with localized and locally advanced PCa. Diagnostic accuracy and efficacy as a prognostic factor of biochemical recurrence of plasma hTERT mRNA were determined using univariate and multivariate analyses and compared with conventional tumor markers. Results: Patients with locally advanced disease had significantly (p < 0.05) higher plasma hTERT mRNA and serum PSA levels than those with localized disease. Plasma hTERT mRNA test showed lower sensitivity (83% vs. 100%), higher specificity (73% vs. 43%), AUC ROC curve (0.911 vs. 0.757), and positive likelihood ratios (6.17 vs. 1.76) than the PSA assay in discriminating between localized and locally advanced disease. At multivariate analysis, plasma hTERT mRNA levels and age but not PSA showed a positive trend (p = 0.05) in the risk of locally advanced PCa. On univariate analysis, plasma hTERT mRNA and serum PSA were identified as significant prognostic factors of biochemical recurrence. Using ROC curves and the appropriate cutoff, both tests showed high sensitivity (85%) and specificity (72%). Kaplan-Meier curves confirmed the significant differences between the groups and patients with higher levels than the cutoff value showed diminished recurrence-free survival (p < 0.05). At multivariate analysis, Gleason score and PSA were the strongest factors associated with biochemical recurrence (p < 0.05), whereas hTERT mRNA did not reach statistical significance, although a positive trend was observed (p = 0.09).Conclusion: Plasma hTERT mRNA quantification can be both a useful non-invasive tumor marker for discriminating between localized and locally advanced PCa, as well as a prognostic factor of recurrence at the molecular level.
机译:简介:自从引入前列腺特异性抗原(PSA)测试以来,新的前列腺癌(PCa)患者得到了较早的诊断,并且大多数患有局部和局部晚期疾病。当前的诊断方法缺乏特异性和敏感性,导致对低危器官限定性局部疾病患者的过度诊断和过度治疗。因此,需要新的非侵入性分子工具来区分局部和局部晚期疾病。方法:通过qRT-PCR测定49例局部和局部晚期PCa患者的血浆端粒酶逆转录酶(hTERT)mRNA水平。使用单变量和多变量分析确定诊断准确性和功效作为血浆hTERT mRNA生化复发的预后因素,并将其与常规肿瘤标志物进行比较。结果:局部晚期疾病患者的血浆hTERT mRNA和血清PSA水平显着高于局部疾病患者(p <0.05)。血浆hTERT mRNA测试显示,与PSA相比,灵敏度较低(83%对100%),特异性更高(73%对43%),AUC ROC曲线(0.911对0.757)和似然比(6.17对1.76)鉴别局部疾病和局部晚期疾病的方法。在多变量分析中,血浆hTERT mRNA水平和年龄而非PSA均显示局部晚期PCa风险呈正趋势(p = 0.05)。在单因素分析中,血浆hTERT mRNA和血清PSA被确定为生化复发的重要预后因素。使用ROC曲线和适当的截止值,这两个测试均显示出高灵敏度(85%)和特异性(72%)。 Kaplan-Meier曲线证实两组之间的显着差异以及水平高于临界值的患者显示无复发生存率降低(p <0.05)。在多变量分析中,格里森评分和PSA是与生化复发相关的最强因素(p <0.05),尽管观察到阳性趋势(p = 0.09),但hTERT mRNA并未达到统计学显着性。结论:血浆hTERT mRNA定量可以既可以用作区分局部和局部晚期PCa的有用的非侵入性肿瘤标志物,又可以作为在分子水平上复发的预后因素。

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