Department of Clinical Laboratory, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
J Cell Mol Med. 2020 Dec;24(24):14502-14513. doi: 10.1111/jcmm.16077. Epub 2020 Nov 9.
Dysregulation of small non-coding RNA (ncRNA) is associated with various human diseases including cancer. This study aimed to evaluate the circulating exosomal small RNAs including microRNAs (miRNAs) and P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) as sensitive and specific non-invasive biomarkers for gastric cancer (GC) diagnosis. Serum exosomal small RNA transcriptome was examined using unique molecular identifiers (UMI) small RNA sequencing. Dysregulated miRNAs and piRNAs were verified in 70 GC patients and 60 healthy controls (HC) by reverse transcription quantitative PCR. The expressions of miR-1307-3p, piR-019308, piR-004918 and piR-018569 in serum exosomes were significantly increased in GC group as compared to those in HC group. Moreover, GC patients with metastasis had significantly higher expression levels of piR-004918 and piR-019308 than GC patients without metastasis. The area under the curve (AUC) for miR-1307-3p, piR-019308, piR-004918 and piR-018569 in the GC group was 0.845, 0.820, 0.754 and 0.732, respectively. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 199 can improve the AUC of miR-1307-3p to 0.902 and piR-019308 to 0.914 for GC diagnosis. In conclusion, our findings indicate that serum exosomal piRNAs are promising non-invasive diagnostic biomarkers for GC patients and potential markers for monitoring metastasis.
小非编码 RNA（ncRNA）的失调与包括癌症在内的各种人类疾病有关。本研究旨在评估循环外泌体小 RNA（包括 microRNA（miRNA）和 P 元件诱导的软弱测试（PIWI）相互作用 RNA（piRNA））作为胃癌（GC）诊断的敏感和特异的非侵入性生物标志物。使用独特分子标识符（UMI）小 RNA 测序检查血清外泌体小 RNA 转录组。通过逆转录定量 PCR 验证了 70 名 GC 患者和 60 名健康对照（HC）中的失调 miRNA 和 piRNA。与 HC 组相比，GC 组血清外泌体中 miR-1307-3p、piR-019308、piR-004918 和 piR-018569 的表达显著增加。此外，有转移的 GC 患者的 piR-004918 和 piR-019308 表达水平明显高于无转移的 GC 患者。miR-1307-3p、piR-019308、piR-004918 和 piR-018569 在 GC 组的曲线下面积（AUC）分别为 0.845、0.820、0.754 和 0.732。癌胚抗原（CEA）和糖链抗原（CA）199 的联合应用可将 miR-1307-3p 的 AUC 提高至 0.902，piR-019308 的 AUC 提高至 0.914，用于 GC 诊断。总之，我们的研究结果表明，血清外泌体 piRNA 是 GC 患者有前途的非侵入性诊断生物标志物，也是监测转移的潜在标志物。
