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失调的转运RNA衍生小RNA作为潜在的胃癌生物标志物

Dysregulated transfer RNA-derived small RNAs as potential gastric cancer biomarkers.

作者信息

Yuan Jie, Gu Wenchao, Xu Tianxin, Zhang Yan, Shen Lei, Yan Jianliang, Guan Xi, Chu Haidan, Yuan Ruoyu, Ju Shaoqing

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.

Department of Special Laboratory Center, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.

出版信息

Exp Biol Med (Maywood). 2024 Dec 13;249:10170. doi: 10.3389/ebm.2024.10170. eCollection 2024.

Abstract

Gastric cancer (GC) is the kind of carcinoma that has the highest rates of morbidity and death worldwide. In the early stages of GC, there is currently an absence of sensitive and specific biomarkers. The newly-discovered class of non-coding RNAs (ncRNAs) known as transfer RNA-derived small RNAs (tsRNAs) is highly expressed in bodily fluids and neoplastic cells. High-throughput sequencing was initially employed to identify differentially expressed tsRNAs in early GC patients, followed by validation in patient serum, GC tissues, and cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We identified dysregulated tsRNAs (the up-regulated tsRNAs included tRF-31-PNR8YP9LON4VD, tRF-30-MIF91SS2P4FI, and tRF-30-IK9NJ4S2I7L7, whereas the down-regulated tsRNAs included tRF-38-W6RM7KYUPRENRHD2, tRF-37-LBRY73W0K5KKOV2, tRF-36-JB59V3WD8YQ84VD, tRF-25-MBQ4NKKQBR, and tRF-36-0KFMNKYUHRF867D) in GC, and we verified that the serum of patients, GC cells and tissues both consistently expressed these tsRNAs. Additionally, GC patients' serum had considerably greater expression levels of the three up-regulated tsRNAs than did healthy controls. Receiver operating characteristic (ROC) curve analysis demonstrated that the sensitivity and specificity of the three up-regulated tsRNAs were superior to those of CEA, CA199, and CA724 in the process of diagnosing GC, particularly in its early stages. This suggests that tsRNAs have great diagnostic efficacy and potential as new "liquid biopsy" biomarkers for the diagnosis of GC. Using bioinformatics software, we predicted that dysregulation of tsRNAs may be a potential regulatory mechanism for the development of GC.

摘要

胃癌(GC)是全球发病率和死亡率最高的癌症类型。在胃癌的早期阶段,目前缺乏敏感且特异的生物标志物。新发现的一类非编码RNA(ncRNAs),即转运RNA衍生的小RNA(tsRNAs),在体液和肿瘤细胞中高表达。最初采用高通量测序来鉴定早期胃癌患者中差异表达的tsRNAs,随后通过定量实时聚合酶链反应(qRT-PCR)在患者血清、胃癌组织和细胞系中进行验证。我们在胃癌中鉴定出失调的tsRNAs(上调的tsRNAs包括tRF-31-PNR8YP9LON4VD、tRF-30-MIF91SS2P4FI和tRF-30-IK9NJ4S2I7L7,而下调的tsRNAs包括tRF-38-W6RM7KYUPRENRHD2、tRF-37-LBRY73W0K5KKOV2、tRF-36-JB59V3WD8YQ84VD、tRF-25-MBQ4NKKQBR和tRF-36-0KFMNKYUHRF867D),并且我们验证了患者血清、胃癌细胞和组织均一致表达这些tsRNAs。此外,胃癌患者血清中三种上调的tsRNAs的表达水平明显高于健康对照。受试者工作特征(ROC)曲线分析表明,在胃癌诊断过程中,尤其是早期阶段,三种上调的tsRNAs的敏感性和特异性优于癌胚抗原(CEA)、糖类抗原199(CA199)和糖类抗原724(CA724)。这表明tsRNAs作为诊断胃癌的新型“液体活检”生物标志物具有巨大的诊断效能和潜力。使用生物信息学软件,我们预测tsRNAs的失调可能是胃癌发生发展的一种潜在调控机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed35/11673218/75171ebd79a4/ebm-249-10170-g001.jpg

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