Urinary Exosomal Long Noncoding RNA TERC as a Noninvasive Diagnostic and Prognostic Biomarker for Bladder Urothelial Carcinoma.

Urinary Exosomal Long Noncoding RNA TERC as a Noninvasive Diagnostic and Prognostic Biomarker for Bladder Urothelial Carcinoma.
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尿外泌体长非编码 RNA TERC 作为膀胱尿路上皮癌的无创诊断和预后生物标志物

DOI:
10.1155/2022/9038808
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发表时间:
2022
影响因子:
4.1
通讯作者:
Li D
Li D
中科院分区:
医学3区
文献类型:
--
作者:
Chen C;Shang A;Sun Z;Gao Y;Huang J;Ping Y;Chang W;Gu C;Sun J;Ji P;Yuan Y;Lu R;Li D

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膀胱癌是世界范围内最常见的泌尿系统恶性肿瘤之一,大约90%的膀胱癌病例在组织学上被分型为膀胱尿路上皮癌(BLCA)。外泌体是30至200 nm的细胞外囊泡,其跨组织和通过循环运输microRNA、长非编码RNA(lncRNA)、mRNA、环状RNA和蛋白质。尿外泌体可能含有来自肿瘤细胞的遗传信息。在此,我们探讨了尿外泌体lncRNA端粒酶RNA组分(TERC)水平的临床意义,以提供一个急需的诊断和预后生物标志物BLCA。 在这项研究中,我们使用来自四名BLCA患者和三名健康对照的样本的RNA测序来鉴定TERC在尿外泌体中的差异表达。然后,我们在不同类型的临床样本中使用定量PCR来验证生物标志物,并使用受试者工作特征曲线分析结果。 我们发现,与健康对照组相比,BLCA患者的尿外泌体中TERC显著上调(P < 0.0001)。尿外泌体TERC检测的敏感性(78.65%)和准确性(77.78%)均高于核基质蛋白-22和尿细胞计数等指标。以4.302为界值,尿外泌体TERC曲线下面积为0.836(95%可信区间:0.768-0.891,P < 0.0001)。此外,这种非侵入性检测可以区分低级别和高级别肿瘤(P = 0.0153)。 TERC在来自BLCA患者的尿外泌体中富集。尿外泌体TERC可能成为BLCA的诊断和预后生物标志物,使临床医生能够实现BLCA的无创检测。
Bladder cancer is one of the most common urological malignancies worldwide, and approximately 90% of bladder cancer cases are histologically typed as bladder urothelial carcinoma (BLCA). Exosomes are 30 to 200 nm extracellular vesicles that transport microRNAs, long noncoding RNAs (lncRNAs), mRNAs, circular RNAs, and proteins across tissues and through circulation. Urinary exosomes may contain genetic information from tumor cells. Herein, we explored the clinical significance of urinary exosomal lncRNA telomerase RNA component (TERC) levels to provide an urgently needed diagnostic and prognostic biomarker for BLCA. In this study, we used RNA-sequencing of samples from four BLCA patients and three healthy controls to identify that TERC was differentially expressed in urinary exosomes. We then used quantitative PCR in different types of clinical samples to validate the biomarker and analyzed results using receiver operating characteristic curves. We found that TERC was significantly upregulated in urinary exosomes from BLCA patients compared with those from healthy controls (P < 0.0001). Urinary exosomal TERC showed higher sensitivity (78.65%) and accuracy (77.78%) than existing indicators including nuclear matrix protein-22 and urine cytometry. Using the cut-off value 4.302, the area under the curve for urinary exosomal TERC was 0.836 (95% confidence interval: 0.768–0.891, P < 0.0001). Furthermore, this noninvasive assay could distinguish low-grade and high-grade tumors (P = 0.0153). TERC is enriched in urinary exosomes from BLCA patients. Urinary exosomal TERC could become a diagnostic and prognostic biomarker for BLCA that allows clinicians to realize noninvasive detection of BLCA.
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