Identification of Serum Circulating MicroRNAs as Novel Diagnostic Biomarkers of Gastric Cancer

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-associated deaths worldwide. Due to the lack of typical symptoms and effective biomarkers for non-invasive screening, most patients develop advanced-stage GC by the time of diagnosis. Circulating microRNA (miRNA)-based panels have been reported as a promising tool for the screening of certain types of cancers. In this study, we performed differential expression analysis of miRNA profiles of plasma samples obtained from gastric cancer and non-cancer patients using two independent Gene Expression Omnibus (GEO) datasets: GSE113486 and GSE124158. We identified three miRNAs, hsa-miR-320a, hsa-miR-1260b, and hsa-miR-6515-5p, to distinguish gastric cancer cases from non-cancer controls. The three miRNAs showed an area under the curve (AUC) over 0.95 with high specificity (>93.0%) and sensitivity (>85.0%) in both the discovery datasets. In addition, we further validated these three miRNAs in two external datasets: GSE106817 [sensitivity: hsa-miR-320a (99.1%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (92.2%); specificity: hsa-miR-320a (88.8%), hsa-miR-1260b (89.6%), and hsa-miR-6515-5p (88.7%); and AUC: hsa-miR-320a (96.3%), hsa-miR-1260b (97.4%), and hsa-miR-6515-5p (94.6%)] and GSE112264 [sensitivity: hsa-miR-320a (100.0%), hsa-miR-1260b (98.0%), and hsa-miR-6515.5p (98.0%); specificity: hsa-miR-320a (100.0%), hsa-miR-1260b (100.0%), and hsa-miR-6515.5p (92.7%); and AUC: hsa-miR-320a (1.000), hsa-miR-1260b (1.000), and hsa-miR-6515-5p (0.988)]. On the basis of these findings, the three miRNAs can be used as potential biomarkers for gastric cancer screening, which can provide patients with a higher chance of curative resection and longer survival.

Identifying Potential miRNA Biomarkers for Gastric Cancer Diagnosis Using Machine Learning Variable Selection Approach

“…We also found three other miRNAs (hsa-miR-8073 and hsa-miR-1228-5p) with a great contribution to the GC prediction. A medical expert can use these findings for the early detection of GC instead of using costly and timeconsuming tools such as colonoscopy Yao et al (Yao, 2020). This study had several strengths compared to the previous studies.…”

“…Considering the important role of GC early diagnosis in patient’s survival rate and the lack of published article on identifying potential miRNAs for GC prediction at an early stage by AT, the present study aims to identify the potential miRNA for predicting GC by AT in the datasets of Gene Expression Omnibus (GEO) specifically with the stat of the art machine learning models. Traditional statistical models such as linear models previously has been used in looking for GC biomarkers and identified miRNAs with the potential prediction power ( Yao, 2020 ), however, they have not implemented advanced methods such as machine learning and new variable selection approaches such as Synthetic Minority Oversampling Technique (SMOTE). In the present study, for the first time, we aimed to use those new techniques for identification of GC related miRNAs with a reliable cut-of and highest possible accurecy in the external validation.…”

Knockdown of miR‐125b‐5p inhibits the proliferation and invasion of gastric carcinoma cells by targeting RYBP

“…Multiple lines of evidence have verified that miRNAs have clinical importance in gastric carcinoma, aiding its diagnosis, prognosis, and management. 16,17 Five miRNA signatures (miR-1, miR-20, miR-27a, miR-34, and miR-423-5p) have been identified as the diagnostic markers for gastric cancer with the receiver operating characteristic curve over 0.85% in serum samples, demonstrating higher sensitivity than conventional markers (CEA or CA19-9). 18 The involvement of miRNAs in gastric carcinoma pathogenesis has been documented as well.…”

Biomarkers for Gastric Cancer Screening and Early Diagnosis

“…In the whole study, 235 GC patients and 3174 healthy controls were analyzed, reflecting a real-life scenario, where the proportion of GC among healthy individuals is low. However, despite these promising data, it would be interesting to further evaluate these miRNAs in early GC patients, GC premalignant lesions, and other types of cancer to determine if they can be found at these less advanced stages and if they are exclusive for GC or not [26].…”