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

Abstract

Cancer represents a group of heterogeneous diseases that are a leading global cause of death. Even though mortality has decreased in the past thirty years for different reasons, most patients are still diagnosed at the advanced stage, with limited therapeutic choices and poor outcomes. Moreover, the majority of cancers are detected using invasive painful methods, such as endoscopic biopsy, making the development of non-invasive or minimally invasive methods for the discovery and fast detection of specific biomarkers a crucial need. Among body fluids, a valuable non-invasive alternative to tissue biopsy, the most accessible and least invasive are undoubtedly urine and saliva. They are easily retrievable complex fluids containing a large variety of endogenous compounds that may provide information on the physiological condition of the body. The combined analysis of these fluids with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS), a reliable and easy-to-use instrumentation that provides information with relatively simple sample pretreatments, could represent the ideal option to rapidly achieve fast early stage diagnosis of tumors and their real-time monitoring. On this basis, the present review summarizes the recently reported applications relevant to the MALDI analysis of human urine and saliva samples.

Advancements in Oncoproteomics Technologies: Treading toward Translation into Clinical Practice

“…The ability to desorb large molecules, high accuracy, high sensitivity, and wide mass range makes MALDI-TOF MS a method of choice in clinical settings for the identification of biomolecules in complexes [ 66 , 67 ] and cancer diagnosis and prognosis [ 68 ]. For instance, MALDI-TOF MS is used in differentiating ovarian cancer from healthy controls.…”

Algorithms push forward the application of MALDI–TOF mass fingerprinting in rapid precise diagnosis

“…78 It can be achieved by pretreatment of the specimens using strategies like differential centrifugation, affinity capture, magnetic precipitation, microchip separation, in-situ extraction, chromatography, and so on. [79][80][81][82][83] A large number of patient specimens are also required to establish reliable machine learning classifiers with sufficient enough learning data.…”

“…The success of such a biomarker discovery methodology relies heavily on the samples pretreatment procedures to obtain as many mass peaks as possible, especially the peaks from low‐abundant proteins and peptides 78 . It can be achieved by pretreatment of the specimens using strategies like differential centrifugation, affinity capture, magnetic precipitation, microchip separation, in‐situ extraction, chromatography, and so on 79–83 . A large number of patient specimens are also required to establish reliable machine learning classifiers with sufficient enough learning data.…”

Proteomics-Based Identification of Dysregulated Proteins in Breast Cancer

“…Almost 27% of the whole-saliva proteins have been also identified in plasma [ 230 ]. Several MS-based approaches have been applied to detect salivary peptides, such as SELDI-TOF MS [ 231 ], [ 232 ], ESI-TOF MS, MALDI-TOF MS [ 233 ], ESI-Orbitrap MS, and ESI-Q-TOF MS [ 234 ]. The top-down analysis of undigested proteins has usually been performed using MALDI mass spectrometers, while the majority of digested proteins/peptides detections was performed using ESI ionization with TOF and Orbitrap mass analyzers [ 234 ].…”