Abstract
Patients with gastric cancer (GC) are usually first diagnosed at an advanced stage due to the absence of obvious symptoms at an early GC (EGC) stage. Therefore, it is necessary to identify an effective screening method to detect precursor lesions of GC (PLGC) and EGC to increase the 5-year survival rate of patients. Cell-free RNA, as a biomarker, has shown potential in early diagnosis, personalised treatment, and prognosis of cancer. In this study, six RNAs (CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18) were analysed via real-time quantitative polymerase chain reaction (RT-qPCR) using the plasma of patients with EGC and PLGC to identify diagnostic biomarkers. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy. Among the six RNAs, four lncRNAs (CEBPA-AS1, INHBA-AS1, AK001058, and UCA1) were upregulated and two mRNAs (PPBP and RGS18) were downregulated in the plasma of patients with PLGC and EGC. According to the findings of the ROC analysis, the four-RNA combination of INHBA-AS1, AK001058, UCA1, and RGS18 had the highest area under the curve (AUC) value for determining risk of GC in patients with PLGC and the six-RNA combination including CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18 had the highest AUC value for determining the risk of GC in patients with EGC. The results suggest the potential usefulness of noninvasive biomarkers for the molecular diagnosis of GC at earlier stages.
Highlights
Gastric cancer (GC) is the fifth most common malignant tumour and the fourth leading cause of cancer-related death globally
To test whether the traditional tumour markers could be used for the prediction of risk of GC in early GC (EGC) and precursor lesions of GC (PLGC), we examined the levels of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), and carbohydrate antigen 19-9 (CA19-9) in plasma of patients with EGC and PLGC (Tables S4)
We found lower positive rates for single and combined tumour markers in patients with PLGC than patients with EGC (Table 2). e positive rates of these tumour markers in both groups were lower than previously reported positive rates of tumour markers in GC patients with CEA (21.8%), AFP (5.0%), CA19-9 (24.4%), and their combinations (47.1%, including CA125) [26], which indicated that the traditional markers are unsuitable for the prediction of the risk of GC in patients with EGC and PLGC
Summary
Gastric cancer (GC) is the fifth most common malignant tumour and the fourth leading cause of cancer-related death globally. Gastroscopy combined with tissue biopsy is the “gold standard” method for tumour detection and diagnosis, endoscopy is limited by the type of equipment and physician techniques and the results vary [3]. CfRNAs obtained from the plasma and serum as biomarkers for detecting and diagnosing EGC [12,13], such as lncRNA PCGEM1 and UCA1 [14,15]; circRNA circ_0141633 and circ_0004771 [16,17]; miRNA miR-21 and miR-26a [18,19]; mRNA SLC6A3 and L1CAM [20,21]; and combinations of lncRNAs [22], miRNAs [23], and mRNAs [24]. We investigated the expression of four lncRNAs and two mRNAs in the plasma of patients with EGC and precursor lesions of GC (PLGC) using realtime quantitative polymerase chain reaction (RT-qPCR). Our study indicated that the combination of plasma lncRNA and mRNA expression might be a useful biomarker for GC diagnosis
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