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RNA测序分析确定了血清中的一个三lncRNA组合作为肌肉浸润性膀胱癌的潜在生物标志物。

RNA-seq profiling identified a three-lncRNA panel in serum as potential biomarker for muscle-invasive bladder cancer.

作者信息

Jiang Xiumei, Qu Ailin, Zhang Shoucai, Jin Shuchao, Wang Lishui, Zhang Yi

机构信息

Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China.

Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong, China.

出版信息

Front Oncol. 2024 Dec 16;14:1451009. doi: 10.3389/fonc.2024.1451009. eCollection 2024.

Abstract

BACKGROUND

Preoperative determination of muscular infiltration is crucial for appropriate treatment planning in patients with muscle-invasive bladder cancer (MIBC). We aimed to explore early diagnostic biomarkers in serum for MIBC in this study.

METHODS

The expression profiles of long noncoding RNA (lncRNA) were initially screened by high-throughput sequencing and evaluation of potential lncRNAs were conducted by two phases of RT-qPCR assays using serum samples from 190 patients with MIBC and 190 non-muscle-invasive BC (NMIBC) patients. Multivariate logistic regression analysis was applied to establish a diagnostic signature with high accuracy and Fagan's nomogram was plotted to promote clinical application. Bioinformatics analysis was used to determine the potential miRNA-mRNA binding of candidate lncRNAs.

RESULTS

We identified three differentially expressed lncRNAs (LINC00565, LINC00592 and NDUFA6-AS1) and established a 3-lncRNA panel which demonstrated high diagnostic accuracy for MIBC with an AUC of 0.903 (95% CI: 0.850-0.942) and 0.875 (95% CI: 0.802-0.928) in the training and validation set. Moreover, construction and assessment of Fagan'nomogram demonstrated that the 3-lncRNA panel could exhibit practical and helpful values for clinical use. Finally, a network map based on LINC00565 was constructed and we found that the expression of miR-143-5p and miR-4516 were significantly correlated with LINC00565 in MIBC.

CONCLUSION

Our findings indicated that the constructed 3-lncRNA panel in serum showed favorable diagnostic capacity and might serve as promising non-invasive biomarkers in the early diagnosis of MIBC.

摘要

背景

术前确定肌肉浸润情况对于肌肉浸润性膀胱癌(MIBC)患者的合理治疗规划至关重要。本研究旨在探索血清中MIBC的早期诊断生物标志物。

方法

最初通过高通量测序筛选长链非编码RNA(lncRNA)的表达谱,并使用190例MIBC患者和190例非肌肉浸润性膀胱癌(NMIBC)患者的血清样本,通过两阶段的RT-qPCR分析对潜在的lncRNA进行评估。应用多变量逻辑回归分析建立具有高准确性的诊断特征,并绘制Fagan列线图以促进临床应用。利用生物信息学分析确定候选lncRNA的潜在miRNA-mRNA结合情况。

结果

我们鉴定出三种差异表达的lncRNA(LINC00565、LINC00592和NDUFA6-AS1),并建立了一个由三个lncRNA组成的panel,其对MIBC具有较高的诊断准确性,在训练集和验证集中的AUC分别为0.903(95%CI:0.850-0.942)和0.875(95%CI:0.802-0.928)。此外,Fagan列线图的构建和评估表明,该由三个lncRNA组成的panel在临床应用中具有实用且有帮助的价值。最后,构建了基于LINC00565的网络图,我们发现miR-143-5p和miR-4516的表达与MIBC中LINC00565显著相关。

结论

我们的研究结果表明,构建的血清中由三个lncRNA组成的panel具有良好的诊断能力,可能成为MIBC早期诊断中有前景的非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e969/11683095/5a6896303700/fonc-14-1451009-g001.jpg

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