血清中携带NSD1和FBXO7 mRNA的细胞外囊泡作为胃癌的新型生物标志物。
Serum extracellular vesicles with NSD1 and FBXO7 mRNA as novel biomarkers for gastric cancer.
发表日期:2023 Sep 22
作者:
Zhen Wang, Juan Ding, Yilei Xiao, Ke Xiao, Ping Su, Zhaogang Dong, Yi Zhang
来源:
GENES & DEVELOPMENT
摘要:
血清细胞外囊泡(EVs)中的信使RNA(mRNAs)是各种癌症的有效无创生物标志物,然而,它们作为胃癌标志物的角色尚待研究。因此,本研究旨在探索它们作为胃癌新型生物标志物的潜力。对4例胃癌患者和4例健康对照者的血清EVs中的mRNAs进行了研究。提取血清EVs中的mRNAs进行高通量RNA测序(RNA-seq)。进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,以预测与癌症相关的基因。使用逆转录定量聚合酶链反应对候选mRNAs进行验证。通过受试者工作特征(ROC)曲线和Kaplan-Meier分析评估mRNAs在胃癌中的诊断和预后价值。RNA-seq揭示了在血清EVs中有13,229个上调和7,079个下调的mRNAs。GO和KEGG分析显示某些mRNAs与肿瘤发生和进展相关。其中,根据我们的标准选择了10个(|折叠变化| > 10,P < 0.05)。与健康对照组相比,胃癌患者中NSD1上调而FBXO7下调。这两个mRNAs结合的ROC曲线下面积为0.84,灵敏度为78%,特异度为92%。NSD1和FBXO7还与肿瘤大小、远处转移和TNM分期有关。此外,NSD1表达与预后密切相关,根据我们的随访研究和在线数据库分析得出。然而,FBXO7只在我们的随访数据中与预后显著相关。血清EVs中的NSD1和FBXO7在胃癌中具有重要作用,可作为其诊断和预后的有用生物标志物。版权所有 © 2023年。由Elsevier Inc发表。
Messenger RNAs (mRNAs) in serum extracellular vesicles (EVs) are effective non-invasive biomarkers for various types of cancer, however, their role as biomarkers for gastric cancer is yet to be investigated. Therefore, the current study was designed to explore their potential as novel biomarkers for gastric cancer..The mRNAs in serum EVs from four patients with gastric cancer and four healthy controls were investigated. mRNAs in serum EVs were extracted for high-throughput RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict cancer-related genes. Candidate mRNAs were validated using reverse transcription-quantitative polymerase chain reaction. The diagnostic and prognostic values of mRNAs for gastric cancer were evaluated by receiver operating characteristic (ROC) curves and Kaplan-Meier analysis, respectively.RNA-seq revealed 13,229 upregulated and 7,079 downregulated mRNAs in serum EVs. GO and KEGG analyses showed that certain mRNAs were associated with tumorigenesis and progression. From these, 10 were selected according to our criteria (|Fold Change| > 10, P < 0.05). NSD1 was upregulated and FBXO7 was downregulated in patients with gastric cancer compared with the healthy controls. The area under the ROC curves of these two mRNAs combined was 0.84, with a sensitivity of 78% and a specificity of 92%. NSD1 and FBXO7 were also associated with tumor size, distal metastasis, and TNM stage. Furthermore, NSD1 expression was strongly associated with prognosis, as revealed from our follow-up studies and online database analysis. However, FBXO7 was only significantly associated with prognosis in our follow-up data.NSD1 and FBXO7 in serum EVs have important roles in gastric cancer and may be useful biomarkers for its diagnosis and prognosis.Copyright © 2023. Published by Elsevier Inc.