基于 mirs-410-3p 和 141-5p 检测的前列腺癌演变诊断新方案

Maria Fernanda Carbache, EVELIN RAQUEL NUNEZ, YOUNESS OUAHID, ENRIQUE SAINZ, JUAN JOSE MONTOYA, ANA MOLERA, AURA SOOUTO, DAVID VAZQUEZ, PABLO CASTAN, JOAQUIN CARBALLIDO
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In this context, a new set of small RNA biomarkers are surfacing with promising results to predict\ntumour progression, risk reclassification and treatment response(2) such as miR-410-3p -3p and miR-141-5p.\nFormer studies where these biomarkers were examined in prostate cancer tissues and cell lines by qRT-PCR\nhave shown that high expression of miR-410-3p -3p correlates to both a) accurate diagnosis in certain groups\nwhere the PSA levels do not match results from biopsy, surgery and/or digital rectal examination and b) poor\nprognosis of prostate cancer patients(3) . Likewise, miR-141-5p shows a parallel behaviour suggesting a potential\ncombo for fine molecular analysis of the ratios. In this sense, recent studies have demonstrated that miR-410-3p\n-3p exert oncogenic functions through downregulating PTEN, proving that miR-410-3p -3p inhibits prostate\ncancer progression via downregulating PTEN/AKT/mTOR signalling pathway. 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引用次数: 0

摘要

迄今为止,前列腺癌(PCa)既是男性最常见的肿瘤,也是导致癌症相关死亡的第二大原因(1, )。事实证明,预防计划和筛查方案有助于在人群中发现该疾病,但与常规用于筛查其他类型癌症的分子检测相比,它们缺乏灵敏度和特异性,导致许多病例进行不必要的活检和过度治疗。在这种情况下,一组新的小 RNA 生物标志物正在浮出水面,它们在预测肿瘤进展、风险再分类和治疗反应(2)方面取得了可喜的成果,如 miR-410-3p -3p 和 miR-141-5p。以前通过 qRT-PCR 对前列腺癌组织和细胞系中的这些生物标志物进行检测的研究表明,miR-410-3p -3p 的高表达与以下两个方面有关:a) 某些群体中 PSA 水平与活检、手术和/或数字直肠检查结果不一致时的准确诊断;b) 前列腺癌患者的不良预后(3)。同样,miR-141-5p 也显示出类似的行为,表明它有可能成为对比率进行精细分子分析的组合。从这个意义上说,最近的研究表明,miR-410-3p-3p 通过下调 PTEN 发挥致癌功能,证明了 miR-410-3p -3p 通过下调 PTEN/AKT/mTOR 信号通路抑制前列腺癌的进展。奇怪的是,在患者外周血和癌细胞系(34.5.6)模型中,该生物标记物的行为都不同,这进一步说明了通过并行半定量 miR-141-5p 实现双重测量的优势。从这个意义上说,miR-141-5p 已被明确鉴定为在大型前列腺癌患者队列(n 超过 500)中上调,并在肿瘤上皮和肿瘤基质的多变量分析中证实了过表达。在一项超过 500 名患者的独立研究中,这种过表达与外周血中 miR-410-3p 的减少似乎与生化癌症复发风险的增加有关(7)。在这里,我们介绍了一种新型系统的设计、分子设置和临床前评估,该系统利用 PSA 血液检测中的弃血量,通过检测生物标记物来预测前列腺癌的进展和生化癌复发。所述方法有可能消除对活检、手术和数字直肠检查等侵入性手段的需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
NOVEL SOLUTION BASED ON DETECTION OF MIRS-410-3P AND 141-5P FOR DIAGNOSTIC OF PROSTATE CANCER EVOLUTION
To date, prostate cancer (PCa) is both the most common tumour diagnosed in males and the second most common cause of cancer-related mortality(1,) . Prevention programs and screening protocols have proven useful to detect the disease at population level, but they lack sensitivity and specificity in comparison to the molecular tests routinely available for screening of other types of cancer, leading to unnecessary biopsies and overtreatment in many cases. In this context, a new set of small RNA biomarkers are surfacing with promising results to predict tumour progression, risk reclassification and treatment response(2) such as miR-410-3p -3p and miR-141-5p. Former studies where these biomarkers were examined in prostate cancer tissues and cell lines by qRT-PCR have shown that high expression of miR-410-3p -3p correlates to both a) accurate diagnosis in certain groups where the PSA levels do not match results from biopsy, surgery and/or digital rectal examination and b) poor prognosis of prostate cancer patients(3) . Likewise, miR-141-5p shows a parallel behaviour suggesting a potential combo for fine molecular analysis of the ratios. In this sense, recent studies have demonstrated that miR-410-3p -3p exert oncogenic functions through downregulating PTEN, proving that miR-410-3p -3p inhibits prostate cancer progression via downregulating PTEN/AKT/mTOR signalling pathway. Curiously enough, different behaviour has been reported for the biomarker in both, peripheral blood from patients and cancer-cell line(s) (34.5.6) models further pointing at the advantages of a dual gauging made possible by parallel semi-quantitation of miR-141-5p. In this sense, miR-141-5p has been clearly identified as to be upregulated in large cohorts (n over 500) of prostate cancer patients confirming overexpression in multivariate analysis in tumour epithelium and tumour stroma. This overexpression taken into the context of a peripheral blood reduction of miR-410-3p appears to be associated with increased risk of biochemical cancer recurrence in an independent study over 500 patients (7) . Here we present the design, molecular set up and preclinical assessment of a novel system that uses the discarded volume from PSA blood tests to predict prostate cancer progression and biochemical cancer recurrence via detection of the biomarkers. The method described could potentially eliminate the need of invasive means such as biopsy, surgery and digital rectal examination.
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