Abstract
Cancer diagnostics based on the detection of protein biomarkers in blood has promising potential for early detection and continuous monitoring of disease. However, the currently available protein biomarkers and assay formats largely fail to live up to expectations, mainly due to insufficient diagnostic specificity. Here, we discuss what kinds of plasma proteins might prove useful as biomarkers of malignant processes in specific organs. We consider the need to search for biomarkers deep down in the lowest reaches of the proteome, below current detection levels. In this regard, we comment on the poor molecular detection sensitivity of current protein assays compared to nucleic acid detection reactions, and we discuss requirements for achieving detection of vanishingly small amounts of proteins, to ensure detection of early stages of malignant growth through liquid biopsy.
Highlights
Liquid biopsy offers the possibility to assess the state of health of specific tissues in the body by detecting their released molecules in accessible body fluids such as blood
It is reasonable at this point to ask whether we have found all useful protein biomarkers, and if current protein assay techniques are able to meet the requirements for liquid biopsy in cancer and other diseases
Where should one look for promising protein markers for liquid biopsy? Many current plasma protein biomarkers, such as proteins related to the coagulation system or cytokines, provide highly relevant information about system-wide states of health, but they do not point to any particular organ as the locus for a disease process, and they can not be considered as markers for liquid biopsy
Summary
Liquid biopsy offers the possibility to assess the state of health of specific tissues in the body by detecting their released molecules in accessible body fluids such as blood. A slowly expanding range of other protein markers is commonly used to detect malignancy, including AFP (alpha-fetoprotein), CA125, CEA (carcinoembryonic antigen), CA15-3, CA199 [2,3,4], and a few more, but their clinical utility is limited, even when they are applied in combination (for a current list of FDA (US Food and Drug Administration)-approved protein biomarkers, see table S1 of Suhre et al, 2020 [5]). It is reasonable at this point to ask whether we have found all useful protein biomarkers, and if current protein assay techniques are able to meet the requirements for liquid biopsy in cancer and other diseases. The purpose of this brief perspective is to argue that we have not been looking in all the right places for suitable protein biomarkers, and the vision provided by current assay techniques may have been too poor to find and evaluate the really good markers—but that there now is hope that all this may be about to change
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