Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation

Abstract

BackgroundGastric cancer (GC) is the third leading cause of cancer-related death worldwide, partially due to the lack of effective screening strategies. Thus, there is a stringent need for non-invasive biomarkers to improve patient diagnostic efficiency in GC.MethodsThis study initially filtered messenger RNAs (mRNAs) as prospective biomarkers through bioinformatics analysis. Clinical validation was conducted using circulating mRNA in plasma from patients with GC. Relationships between expression levels of target genes and clinicopathological characteristics were calculated. Then, associations of these selected biomarkers with overall survival (OS) were analyzed using the Kaplan-Meier plotter online tool.ResultsBased on a comprehensive analysis of transcriptional expression profiles across 5 microarrays, top 3 over- and underexpressed mRNAs in GC were generated. Compared with normal controls, expression levels ofcollagen type VI alpha 3 chain(COL6A3),serpin family H member 1 (SERPINH1)andpleckstrin homology and RhoGEF domain containing G1 (PLEKHG1)were significantly upregulated in GC plasmas. Receiver-operating characteristic (ROC) curves on the diagnostic efficacy of plasmaCOL6A3,SERPINH1andPLEKHG1mRNAs in GC showed that the area under the ROC (AUC) was 0.720, 0.698 and 0.833, respectively. Combined, these three biomarkers showed an elevated AUC of 0.907. Interestingly, the higherCOL6A3level was significantly correlated with lymph node metastasis and poor prognosis in GC patients. High level ofSERPINH1mRNA expression was correlated with advanced age, poor differentiation, lower OS, andPLEKHG1was also associated with poor OS in GC patients.ConclusionOur results suggested that circulatingCOL6A3,SERPINH1andPLEKHG1mRNAs could be putative noninvasive biomarkers for GC diagnosis and prognosis.