Serum extracellular vesicles with NSD1 and FBXO7 mRNA as novel biomarkers for gastric cancer.

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.