Salivary glycopatterns as potential biomarkers for diagnosis of gastric cancer

Abstract

Gastric cancer (GC) is still an extremely severe health issue with high mortality due to the lacking of effective biomarkers. In this study, we aimed to investigate the alterations of salivary protein glycosylation related to GC and assess the possibility of salivary glycopatterns as potential biomarkers for the diagnosis of GC. Firstly, 94 patients with GC (n = 64) and atrophic gastritis (AG) (n = 30), as well as 30 age- and sex-matched healthy volunteers (HV) were enrolled in the test group to probe the difference of salivary glycopatterns using lectin microarrays, the results were validated by saliva microarrays and lectin blotting analysis. Then, the diagnostic model of GC (Model GC) and AG (Model AG) were constructed based on 15 candidate lectins which exhibited significant alterations of salivary glycopattern by logistic stepwise regression. Finally, two diagnostic models were assessed in the validation group including HV (n = 30) and patients with GC (n = 23) and AG (n = 24) and achieved high diagnostic power (Model GC (AUC: 0.89, sensitivity: 0.96 and specificity: 0.80), Model AG (AUC: 0.83, sensitivity: 0.92 and specificity: 0.72)). This study provides pivotal information to distinguish HV, AG and GC based on precise alterations in salivary glycopatterns, which have great potential to be biomarkers for diagnosis of GC.

Alterations in serum protein glycopatterns related to small cell lung cancer, adenocarcinoma and squamous carcinoma of the lung

“…41 In gastric cancer, the glycans recognized by ECA, PSA, PHA-E + L, HHL, PNA, EEL, MPL, and GSL-I showed differential expression. 31 In hepatic carcinoma, the glycans recognized by MAL-II, SNA, WFA, PNA, and AAL showed differential expression. 42 In lung cancer, the alteration in the glycopattern is different from breast cancer, gastric cancer and hepatic carcinoma.…”

“…The original data was further analyzed using Expander 6.0 (http://acgt.cs.tau.ac.il/expander/) to perform hierarchical clustering analysis. [31][32][33]…”

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review

“…Similarly, pancreatic carcinoma is insidious, very aggressive and in most cases diagnosed at a very late stage, being associated to a very poor prognosis (46). With regard to gastric cancer 7 studies were included in the present review (15)(16)(17)25,(47)(48)(49). All of these reported statistically significant results.…”

“…Molecules most frequently investigated were proteins and RNA. Twelve studies (23.5%) were scored as "good" and 11 of these reported statistically significant associations between molecules searched and pathology (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Application of Lectin Microarrays for Biomarker Discovery

“…Outer‐arm fucosylation and core‐fucosylation expression levels of glycans specific for AAL and PSA lectins were downregulated, while that of Gal and GalNAc structures recognized by Peanut agglutinin (PNA), Euonymus europaeus lectin (EEL), MPL, GSL−I, Bandeiraea (Griffonia) simplicifolia lectin−I (BSI), ECA, Glycine max (SBA), and VVA were upregulated in the saliva of gastric cancer patients. They could construct the diagnostic models of gastric cancer and atrophic gastritis with high diagnostic accuracy with the 15 selected lectins …”