Peer Review #1 of "Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation (v0.1)"

Abstract

Background. Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, partially due to 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 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 and 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.