血清细胞外囊泡中的 NSD1 和 FBXO7 mRNA 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.

机构信息

Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.

Department of Neurosurgery, Liaocheng People's Hospital, 67 Dongchangxi Road, Liaocheng 252000, Shandong, China.

出版信息

Clin Biochem. 2023 Oct;120:110653. doi: 10.1016/j.clinbiochem.2023.110653. Epub 2023 Sep 22.

DOI:10.1016/j.clinbiochem.2023.110653

PMID:37742869

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

NSD1 and FBXO7 in serum EVs have important roles in gastric cancer and may be useful biomarkers for its diagnosis and prognosis.

摘要

背景

血清细胞外囊泡（EVs）中的信使 RNA（mRNA）是各种类型癌症有效的非侵入性生物标志物，但它们作为胃癌生物标志物的作用尚未得到研究。因此，本研究旨在探讨其作为胃癌新型生物标志物的潜力。

方法

研究人员检测了 4 例胃癌患者和 4 例健康对照者血清 EVs 中的 mRNA。提取血清 EVs 中的 mRNA 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（RT-qPCR）验证候选 mRNA。通过接收者操作特征（ROC）曲线和 Kaplan-Meier 分析分别评估 mRNA 对胃癌的诊断和预后价值。

结果

RNA-seq 显示血清 EVs 中有 13229 个上调和 7079 个下调的 mRNA。GO 和 KEGG 分析表明，某些 mRNA 与肿瘤发生和进展有关。根据我们的标准，从这些中选择了 10 个（|Fold Change| > 10，P < 0.05）。与健康对照组相比，胃癌患者的 NSD1 上调，FBXO7 下调。这两个 mRNA 联合的 ROC 曲线下面积为 0.84，灵敏度为 78%，特异性为 92%。NSD1 和 FBXO7 也与肿瘤大小、远端转移和 TNM 分期有关。此外，我们的随访研究和在线数据库分析表明，NSD1 表达与预后密切相关。然而，FBXO7 仅在我们的随访数据中与预后显著相关。