Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes

Abstract

Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, ROC analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.

«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer

“…Most studies on the analysis of saliva in breast cancer were aimed at identifying biomarkers that can differentiate patients with breast cancer from healthy controls [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Previously, we identified 11 metabolites that allow us to do this with a sensitivity of up to 91% [ 47 ].…”

“…The literature provides data on the study of the composition of saliva in breast cancer [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Saliva biomarkers have been shown to achieve a sensitivity of 73% (72–74) and a specificity of 74% (72–76) in the diagnosis of breast cancer [ 45 ].…”

Promising applications of human-derived saliva biomarker testing in clinical diagnostics

“…They found fucose levels higher in both cancer samples than in healthy controls, providing preliminary assessment for early diagnosis of tumor. 178 Yang et al have validated the differential expression level of galactosylated N/O-linked glycans in saliva in patients with breast cancer compared with healthy controls, promoting the study for early-stage diagnosis. 179 Similarly, they also found alterations of salivary glycoprotein N-glycan profiles could be potential biomarkers distinguishing breast cancer or benign breast diseases and healthy subjects.…”

MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers

“…Even though urine is particularly suitable in the case of urological tumors, it may also provide information from other organs via plasma obtained through glomerular filtration [ 14 ]. Saliva is a complex fluid produced by the salivary glands and composed of large amounts of secretory proteins, electrolytes, and other age/sex-related substances, which has proved to be a suitable substrate for the detection different types of cancer [ 15 , 16 ]. It can also be easily retrieved and is suitable for repeated testing.…”