Gastric cancer detection by non‐blood‐based liquid biopsies: A systematic review looking into the last decade of research

Abstract

Gastric cancer (GC) screening is arguable in most Western countries. Liquid biopsies are a great promise to answer the unmet need for less invasive diagnostic biomarkers in GC. Thus, we aimed at systematically reviewing the current knowledge on liquid biopsy-based biomarkers in GC screening. A systematic search on PubMed/MEDLINE and Scopus databases was performed on published articles reporting the use of non-blood specimen (saliva, gastric juice [GJ], urine and stool) on GC diagnosis. 3208 records were retrieved by June 2022. After removal of duplicate records, 2379 abstracts were screened, and 84 full texts included in this systematic review. More than 90% of studies were reported on Asian populations.Overall, 9 studies explored stool-, 12 saliva-, and 29 urine-derived biomarkers for GC detection. Additionally, 37 studies, representing the majority, analyzed GJ, focusing on nucleic acid molecules. Several miRNAs and lncRNA molecules have been associated with GC risk, particularly miR-21 (area under the curve [AUC] = 0.97, 95% CI: 0.94-1.00). Considering salivary biomarkers, the best described model in validation sets included the soybean agglutinin and Vicia villosa agglutinin lectins (AUC = 0.89, 95% CI: 0.80-0.99). Most studies in urine carried out metabolomic approaches, with two discriminatory models presenting AUC values superior to 0.97. This systematic review emphasizes the potential role of non-blood-based biomarkers, although further validation, particularly in Western countries, is mandatory, namely for noninvasive screening and/or monitoring, as well as the use of GJ as a tool to enhance upper gastrointestinal endoscopy accuracy.

Liquid biopsy for gastric cancer: Techniques, applications, and future directions

“…This complexity may limit their serial use for monitoring purposes. Table 1 summarizes the main applications, advantages, and limitations of non-blood samples, according to the review by Tivey et al [ 112 ] and recent research articles[ 113 - 115 ].…”

“…A comprehensive systematic review performed by Lopes et al [ 115 ] compiled over 80 articles related to the use of LB for GC detection utilizing non-blood samples. The majority of articles included Asian patients, and they mainly focused on samples of gastric juice and urine, and to a lesser extent, salivary or stool samples.…”

“…Other researchers have analyzed different types of RNA, proteins, amino acids, microbiota, or metabolites in gastric juice, primarily aiming to detect GC and improve the sensitivity of upper gastrointestinal endoscopy. Proteins such as pepsin A and gastricsin, along with miR-21 and miR-133a, have shown promising discriminatory value[ 115 ].…”

“…In urine samples, according to the review by Lopes et al [ 115 ], the markers with the best diagnostic value in isolation were the metabolite glycerol and endothelial lipase. Profiles including combinations of metabolites or amino acids have also been published, showing good diagnostic accuracy in these samples.…”

Circulating Biomarkers for Cancer Detection: Could Salivary microRNAs Be an Opportunity for Ovarian Cancer Diagnostics?

“…The search for miRNA biomarkers is advancing, although, to date, none has yet reached clinical applications [ 81 ]. Papers dealing with salivary miRNAs BMs for PC [ 75 , 76 , 77 , 82 , 83 ], CRC [ 78 , 84 ], LiC [ 79 , 85 ], LC [ 86 ], BC [ 87 ], GC [ 88 , 89 ], and PrC [ 90 , 91 ] are summarized in Table 1 . MiRNAs were detected both as cell free or as exosomal miRNAs, both in saliva alone as well as in other parallel biofluids.…”