Using an Untargeted Metabolomics Approach to Identify Salivary Metabolites in Women with Breast Cancer

Abstract

Metabolic alterations are a hallmark of the malignant transformation in cancer cells, which is characterized by multiple changes in metabolic pathways that are linked to macromolecule synthesis. This study aimed to explore whether salivary metabolites could help discriminate between breast cancer patients and healthy controls. Saliva samples from 23 breast cancer patients and 35 healthy controls were subjected to untargeted metabolomics using liquid chromatography-quadrupole time-of-flight mass spectrometry and a bioinformatics tool (XCMS Online), which revealed 534 compounds, characterized by their retention time in reverse-phase liquid chromatography and by the m/z ratio detected, that were shared by the two groups. Using the METLIN database, 31 compounds that were upregulated in the breast cancer group (p < 0.05) were identified, including seven oligopeptides and six glycerophospholipids (PG14:2, PA32:1, PS28:0, PS40:6, PI31:1, and PI38:7). In addition, pre-treatment and post-treatment saliva samples were analyzed for 10 patients who experienced at least a partial response to their treatment. In these patients, three peptides and PG14:2 were upregulated before but not after treatment. The area under the curve, sensitivity, and specificity for PG14:2 was 0.7329, 65.22%, and 77.14%, respectively. These results provide new information regarding the salivary metabolite profiles of breast cancer patients, which may be useful biomarkers.

Salivary Metabolomics for Oral Cancer Detection: A Narrative Review

“…Non-targeted non-volatile metabolite profiling of saliva revealed the presence of 18 metabolites, such as LysoPC, related to breast cancer [ 34 ]. Seven oligopeptides and six glycerophospholipids showed breast cancer-specific differences [ 35 ]. Metabolomic profiling using total protein and antioxidant enzymes helped the detection of breast cancer in individuals without breast pathologies [ 36 ].…”

“…For non-targeted analyses, hydrophilic metabolites, such as γ-aminobutyric acid, phenylalanine, valine, and lactic acid, of saliva samples of OC patients were analyzed [ 24 ]. A wide variety of metabolites, such as oligopeptides, phosphatidylcholine, and glycerophospholipids, were analyzed in the saliva samples of patients with breast cancer [ 34 , 35 ]. For targeted analyses, salivary OSCC biomarkers, such as choline, betaine, pipecolinic acid, and carnitine, were quantified [ 61 ].…”

Salivary biomarkers in breast cancer diagnosis: A systematic review and diagnostic meta‐analysis

“… 13 , 14 , 15 , 16 , 17 These investigations have proposed a variety of salivary biomarkers, including proteome, metabolome, transcriptome, and reagent‐free biophotonic. 12 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 In fact, intense research in this area has led to the nomenclature of “salivaomics” which describes saliva‐based diagnostics. 12 , 34 Using saliva for diagnosis has many advantages, including easy collection, minimal training requirement for staff, rapid sampling, hassle‐free storage, simplicity of transportation, less sensitivity to clotting, and fewer risks for the health staff.…”

Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model

“…Metabolic reprogramming is recognized as an important hallmark of cancer, reflective of the interplay of the tumor with its microenvironment, and much has been endeavored in describing and understanding TNBC metabolic traits [ 19 ]. In particular, metabolomic strategies have been extensively used to characterize the TNBC metabolome, mostly through the study of cell lines [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], but also of human samples, either patient biofluids (mainly plasma and serum [ 42 , 43 , 44 , 45 , 46 , 47 , 48 ], but also saliva [ 49 ]) and tumor/tissue biopsies [ 44 , 50 , 51 , 52 ] or extracts [ 53 , 54 , 55 ]. In vivo animal studies (e.g., xenograft models [ 56 , 57 , 58 , 59 , 60 ]), however, are still scarce, compared to in vitro reports, despite the capacity of an in vivo animal model to represent the complex response of the whole organism, both to the disease and to therapy [ 61 ].…”

“…In some instances, attempts have been made to correlate in vitro and in vivo metabolic traits of TNBC [ 62 , 63 ]. Reported metabolomic studies have mostly addressed (i) tumor profiling, in the search for biomarkers of diagnosis/prognosis (comparing TNBC tumors with controls [ 45 , 48 , 49 ] or other BC subtypes [ 21 , 22 , 25 , 46 , 52 ]), and (ii) tumor response to novel treatment protocols [ 26 , 28 , 32 , 44 , 60 ]. In addition, the metabolic adaptations of tumors to specific conditions, such as methionine sensitivity (related to tumor cells proliferation) [ 38 ], the expression of the Mucin1 glycoprotein (modulatory role in cancer metabolism) [ 39 ], the depletion of membrane protein myoferlin (and subsequent impact on metastasis extension) [ 63 ], hypoxia [ 40 , 62 ], the extent of glucose metabolism (associated with tumor malignancy) [ 41 ] and breast cancer gene 1 (BRCA1) mutations [ 42 ], have been investigated.…”