The diagnostic and prognostic application of heat shock proteins and their post-translational modifications from liquid biopsies

Abstract

Liquid biopsies contain numerous proteins coming from extracellular vesicles (EVs), be it microvesicles or exosomes, released by both normal and tumour cells, as well as the presence of any circulating tumour cells (CTCs). Such proteins can be used as biomarkers for early diagnosis, prognostic assessment, disease progression monitoring, therapy selection and treatment response, particularly in oncology. EVs have been identified as mediators of cell-to-cell communication in both normal and pathological conditions and suggested to play a role in promoting and maintaining cancer dissemination and progression by altering the tumour microenvironment through immune suppression, angiogenesis and metastasis. One class of proteins garnering particular interest are extracellular heat shock proteins (HSPs) (secreted despite no consensus secretory sequence), and their post-translational modifications (PTMs), which are thought to act as key players in intercellular crosstalk and activation of signalling pathways during stress conditions. This review will focus on how characterising and quantifying these proteins can indicate the condition of the physiological system in a variety of pathological contexts.