BACKGROUND
As one of the most common tumors, gastric cancer (GC) has a high mortality rate, since current examination approaches cannot achieve early diagnosis.
Fusobacterium nucleatum
(Fn) primarily colonized in the oral cavity, has been reported to be involved in the development of gastrointestinal tumor. Until now, little is known about the relationship between salivary Fn and GC.
AIM
To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells.
METHODS
The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients, 31 atrophic gastritis (AG) patients, 35 non-AG (NAG) patients, 26 gastric polyp (GP) patients, and 20 normal controls (NC) from Qilu Hospital of Shandong University from January 2019 to December 2020. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4. Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells. The expression of epithelial-mesenchymal transition (EMT) markers was detected using western blot assay.
RESULTS
We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG, NAG, and GP patients and NC (
P
< 0.001). ROC curve analysis showed a favorable capability of Fn (73.33% sensitivity; 82.14% specificity; area under the curve: 0.813) in GC diagnosis, which was superior to that of CEA, CA19-9, CA72-4, ferritin, and sialic acid. The Fn level in saliva of GC patients was increased as the TNM stage increased. GC patients with lymph node metastasis had higher Fn levels than those without metastasis. Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells. Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin, vimentin, and snail.
CONCLUSION
Fn abundance in saliva could be used as a promising biomarker to diagnose GC, and Fn infection could promote GC metastasis by accelerating the EMT process.
Long non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) are considered to be novel non-invasive biomarkers for gastric cancer (GC). lncRNA colon cancer-associated transcript 1 (CCAT1) is aberrantly expressed in certain types of cancer. However, the role of EV lncRNA CCAT1 in patients with GC remains unclear. The current study aimed to assess the expression levels of lncRNA CCAT1 in the serum EVs of patients with GC and evaluate its potential clinical value. EVs were isolated from serum using a commercial kit and ultracentrifugation, and were identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Serum EV lncRNA CCAT1 levels in patients with GC, chronic gastritis or atypical hyperplasia and healthy control subjects were detected by reverse transcription-quantitative PCR. Additionally, lncRNA CCAT1 was detected in GC and adjacent non-cancerous tissue samples. Serum EVs were successfully isolated and identified in all patients. The results revealed that serum EV lncRNA CCAT1 levels in patients with GC were significantly higher compared with those in healthy controls, patients with chronic gastritis or atypical hyperplasia (all P<0.05). Additionally, EV lncRNA CCAT1 expression levels were significantly different among various groups based on the depth of invasion, distant metastasis and the Tumor-Node-Metastasis stage. The area under the curve (AUC) value of EV lncRNA CCAT1 was 0.890 [95% confidence interval (CI), 0.826–0.937] with 79.6% sensitivity and 92.6% specificity. The combination of EV lncRNA CCAT1 and carcinoembryonic antibody produced an AUC value of 0.910 (95% CI, 0.849–0.951) with the sensitivity and specificity of 80.5 and 92.6%, respectively. In addition, lncRNA CCAT1 was determined to be stable in serum EVs. The expression levels of lncRNA CCAT1 in GC tissue were positively correlated with those in serum EVs, and high levels of lncRNA CCAT1 were associated with a low disease-free survival rate in patients with GC. The results of the present study demonstrated that serum EV lncRNA CCAT1 levels were upregulated in patients with GC compared with those healthy subjects and patients with other illnesses, and may therefore be used as a novel biomarker for this type of cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.