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

Abstract

Background Gastric 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. Methods This 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. Results Based 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 of collagen type VI alpha 3 chain (COL6A3), serpin family H member 1 (SERPINH1) and pleckstrin homology and RhoGEF domain containing G1 (PLEKHG1) were significantly upregulated in GC plasmas. Receiver-operating characteristic (ROC) curves on the diagnostic efficacy of plasma COL6A3, SERPINH1 and PLEKHG1 mRNAs 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 higher COL6A3 level was significantly correlated with lymph node metastasis and poor prognosis in GC patients. High level of SERPINH1 mRNA expression was correlated with advanced age, poor differentiation, lower OS, and PLEKHG1 was also associated with poor OS in GC patients. Conclusion Our results suggested that circulating COL6A3, SERPINH1 and PLEKHG1 mRNAs could be putative noninvasive biomarkers for GC diagnosis and prognosis.

Evaluation of Plasma MMP-9 and VEGF-A mRNAs as Non-invasive Diagnostic Biomarkers in Women with Endometriosis

“…Several studies have reported that MMP-9 can induce invasiveness in the endometrial tissue, leading to the degradation of ECM, invading other locations, and creating ectopic endometriosis lesions (30,31). There are pieces of evidence suggesting that the MMP-9 gene is significantly overexpressed in the endometriosis tissue, which can be expected according to its role in endometriosis pathogenesis (13,27). The elevation of MMP-9 mRNA in the plasma of endometriosis patients, observed in this study, was consistent with the results of previous investigations on the expression MMP-9 in the endometriosis tissue, suggesting its potential as a non-invasive diagnostic biomarker for endometriosis.…”

“…It has been shown that various kinds of RNAs, including mRNAs and non-coding RNAs, can be extracted and detected in body fluids such as plasma and serum (24,25). Indeed, several investigations have shown that cell-free mRNAs in plasma can be promising non-invasive diagnostic tools for cancer (26,27). Hence, in this study, the plasma levels of MMP-9 and VEGF-A mR-NAs, as the genes relevant to endometriosis pathogenesis, were evaluated by RT-qPCR.…”

SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway

“…Zheng et al analyzed the GEO database and showed that SERPINH1 was one of the five hub genes in GC [28]. Cao et al analyzed plasma mRNA profiles of 56 GC patients and 14 healthy individuals in the Oncomine database and demonstrated high SERPINH1 mRNA levels in the GC samples [29]. In this study, we analyzed SERPINH1 mRNA expression in 888 GC and 318 normal gastric mucosal tissues from three public databases (Oncomine, TCGA, and GEO).…”

Identification of Combinations of Plasma lncRNAs and mRNAs as Potential Biomarkers for Precursor Lesions and Early Gastric Cancer

“…Another study reported that the combination of lncRNA H19, MEG3, and miRNA miR-675-5p improved the diagnostic efficiency compared with using each alone [27]. Although previous studies showed that most biomarkers of GC are associated with cancer differentiation [14,17,29,30], and some RNAs in this study including CEBPA-AS1, IHNBA-AS1, and AK001058 exhibited increasing trends with tumour progression, the expressions of these RNAs were not associated with GC differentiation in heathy participants which should be closed to the high differentiation in patients with GC. Our study results suggest the need to consider healthy controls when assessing the relationship between expressions of biomarkers and cancer differentiation.…”