In the last decades we have witnessed a huge advance in tumor diagnosis and treatment. Overall survival of most tumor patients has increased significantly in recent years and early diagnosis methods emerge rapidly nowadays. However, there are aggressive tumor types that still hide from early diagnosis and do not respond to current treatments. In Fastbase Solutions we concentrate our experience in science research to develop innovative and precise diagnosis methods that could help to improve treatment options for these patients. QF-Pro® is our innovative diagnosis platform that not only detects the presence/absence of tumor markers in a biopsy but also their activity. This information is very valuable for pathologists and oncologists in order to make a precise diagnosis and determine the most efficient treatment.
QF-Pro® comes from the words: Quantitative Functional Proteomics platform, but what do these words mean?
Let’s go word for word in order to understand exactly the features of this platform:
QF-PRO® as a diagnosis platform is able to quantify the level of protein-protein interactions and protein post-translational modifications detected in a given biopsy, providing a quantitative score as a result. In contrast to traditional diagnosis platforms which only give a YES/NO result that should be qualitatively studied by a pathologist, QF-Pro® gives a score to each sample which makes it easier to set a threshold for treatment decisions. Moreover, it also provides with a precise information of the spatio-temporal distribution of these events in the tumor microenvironment,
Despite measuring protein-protein interactions and post-translational modifications is common in basic science, there is not a mean to detect and quantify these functional features of proteins in tissues and biopsies. This fact implies that the results obtained with QF-Pro® are useful not only for basic science and drug development but, moreover, for real diagnosis and treatment decisions.
A protein is a biomolecule comprised of one or more long chains of amino acids that develops an essential function within an organism. Most of the human genes encode the information of proteins. Wilkins et al. proposed in 1995 the term proteome to identify the overall protein content of a cell that is characterized with regards to their localization, interactions, post-translational modifications and turnover, at a particular time1,2. Afterwards, the term “proteomics” emerged to identify all the methods and strategies used for the large-scale study of proteins3. To shed some light on these concepts and try to make them easier for the reader, a protein is a molecule that carries out a function in a cell, the proteome contains all the proteins that are expressed in a given cell in a given moment and proteomics are the methods used to study and define the proteosome.
Since our diagnosis platform QF-Pro® serves to identify proteins and quantify their interactions in patient samples, it is a breakthrough quantitative proteomic tool applied in the field of diagnostic and medicine.
Thereby, we present a diagnosis platform functional for the diagnosis of cancer that uses proteomics to quantify protein interactions and post translational modifications in tumor biopsies.
How does QF-Pro® work?
When a tumor biopsy arrives to the pathology department of a hospital, antibodies are used to detect the presence of tumor markers. With that information the pathologist determines the cancer type and discusses with the oncologist the treatment options. However, even though the presence/absence of a tumor marker gives a lot of information about the tumor type, it could be not enough to define the treatment approach.
Some proteins could remain in our cells in an inactive status. If one of these proteins is a tumor marker, giving a treatment against that protein will not be effective. Thereby, it is very important to know the activity status of tumor markers before deciding the treatment. This fact is especially important when talking about immunotherapy. Tumors can evade the immune response by interacting with our lymphocytes through some receptors called immune checkpoints. To achieve this, tumor cells should express in their surface some proteins that are recognized by a complementary receptor in the surface of the lymphocytes. When this recognition occurs and both surface proteins interact, the immune response is deactivated, and tumor cells can continue proliferating. One example of these surface proteins are PD-1, in the lymphocyte, and PD-L1, in the tumor cell. The treatments known as immunotherapy blockade the interaction of the immune checkpoint avoiding the recognition of the tumor cells and enhancing the immune response. However, this is not the only way tumor cells have to overcome our immune system. Hence, before starting any immunotherapy treatment, it is important to be sure that the immune checkpoint targeted is actually active. Otherwise the treatment will not be effective.
QF-Pro® uses specific antibodies for the recognition of tumor markers such as PD-1 and PD-L1. When these antibodies are attached to their target protein and these proteins are interacting (distance <10nm), the chromophores included in the QF-Pro® antibodies interact resulting in a visible signal. In contrast, when these two proteins are not interacting, and thereby they are not close, the chromophores of the antibodies cannot interact and there is no visible signal. By quantifying the visible signals, we can establish the activation status of the immune checkpoint.
QF-Pro® is not only useful in cancer diagnosis. It can also help to detect protein-protein interactions in many other diseases.
The protein-protein interaction as a measure to help in tumor diagnosis and treatment has previously been suggested and motivated the development of other diagnosis platforms. However, these technologies have only been able to detect close proximity between two proteins rather than direct interaction. QF-Pro® is the first reliable diagnosis method able to address the activation status of tumor markers.
1. Aslam B, Basit M, Nisar MA, Khurshid M, Rasool MH. Proteomics: Technologies and Their Applications. J Chromatogr Sci. 2017 Feb;55(2):182-196.
2. Wilkins MR, Pasquali C, Appel RD, Ou K, Golaz O, Sanchez JC, Yan JX, Gooley AA, Hughes G, Humphery-Smith I, Williams KL, Hochstrasser DF. From proteins to proteomes: large scale protein identification by two-dimensional electrophoresis and amino acid analysis. Biotechnology (N Y). 1996 Jan;14(1):61-5.
3 Wilkins MR, Sanchez JC, Gooley AA, Appel RD, Humphery-Smith I, Hochstrasser DF, Williams KL. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol Genet Eng Rev. 1996;13:19-50.