Identification of plasma exosomal lncRNA as a biomarker for early diagnosis of gastric cancer

Abstract Background, there were about 1,090,000 gastric cancer(GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers. Methods, in this study, the exosomes in the plasma of patients with early gastric cancer were isolated by a commercial kit. After identified by electron microscopy observation, particle size analysis and western-blot verification, the lncRNAs in the exosomes were extracted. The lncRNAs differentially expressed in the plasma exosomes of patients with gastric cancer were analysized by high-throughput RNA sequencing(RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls. Results, Electron microscopy, particle size analysis and western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were up-regulated and 260 lncRNAs were down regulated in plasma exosomes of early gastric cancer patients compared with normal controls. RT-qPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590,Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg. 907985.2,)(p < 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p < 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71). Conclusion, lncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer.