Discovery of tumor markers through platelet proteomics

A crucial element in the process of tumor growth and progression is
angiogenesis, the formation of new blood vessels. Although far from fully
understood, there is currently a large body of documentation on plasma and
serum levels of various angiogenesis regulatory proteins and their predictive
and prognostic values. However, the measurement of growth factors and their use
as a diagnostic have proved to be difficult, as plasma levels of these agents
are only elevated when there is a very high tumor burden. While clearly
associated to parameters of cancer growth and progression, the value of these
angiogenesis factors and their use as biomarkers for prognosis, has thus far
been limited.

Over the last decade it has become clear that platelets may also play an
important role in (tumor) angiogenesis and malignancies. Platelets contain a
broad spectrum of angiogenesis regulating proteins, both pro- and
anti-angiogenic, which they actively take up from plasma and sequester in
platelet granules. In addition, various mouse models have shown that
concentrations of angiogenesis regulatory factors in platelets are modified by
the presence of malignant tumor growth. Even microscopic (<1.0mm)
non-angiogenic tumors have been shown to have a significant effect on the
angiogenic and angiostatic content of platelets.

The objective of the study is to identify potential platelet-derived angiogenic
and angiostatic tumorbiomarkers.
Initially platelet proteomics will be used to detect potential tumormarkers.
Subsequently, these potential tumorbiomarkers will be confirmed with an ELISA
(Enzyme-linked Immunosorbent Assay) in platelets and platelet free plasma of
150 patients who are already being included in a different studie (the *eTA-
study onderzoeksproject nr. 114117).

In this observational study a total of 20 healthy individuals and 20 patients
with stage I&II lung and pancreatic cancer will be included. From the patients
20ml of blood is collected before and after surgery. 10 ml is separated in
platelet pellet and platelet free plasma and stored at -80°C until ELISA. The
remaining 10ml of blood will be used for proteomics to find potential
platelet-derived tumor biomarkers. The potential tumor biomarkers found will be
confirmed with an ELISA (Enzyme-linked Immunosorbent Assay) in platelets and
platelet free plasma of 150 patients who are already included in a different
studie (the *eTA-study onderzoeksproject nr. 114117).

The aim is to keep the extent of the burden and risks to a minimum. Therefore,
the first blood collection is performed during regular blood collection. This
prevents extra vena puncture. The second blood collection occurs two months
after the operation. To minimize the burden, patients are offered to give blood
at home. In this case the researcher will visit them at home to collect blood.
Patients can also choose to come to the hospital to given blood.

The risks are the same as during regular blood drawing using vena puncture.
There is a slight chance of hematoma development. No other risks of
disadvantages are known for this research.