Exploring the molecular mechanisms underlying pre-diagnostic thrombocytosis in lung cancer patients and evaluating its diagnostic value

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Thrombocytosis (i.e. a platelet count of over 400 x 109/l in peripheral blood) has been described in cancer patients by several studies. A recent epidemiological study by the main applicant was the first to discover that thrombocytosis is a risk marker for undiagnosed cancer, and has particularly high value as a predictive marker for lung cancer development, although the study did not differentiate between different lung cancer types. The biological mechanisms underlying this association are poorly understood. Over 46,000 new lung cancers are diagnosed in the UK annually with over 36,000 deaths. Diagnosis is generally made with advanced staging, though early staging may be amenable to curative surgery.In the project proposed for this studentship, we aim to evaluate the association of thrombocytosis with a future diagnosis (within 12 months) of different types of lung cancer in UK primary care records (adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell lung cancer or SCLC). Subsequently, cell lines of the above cancer types will be tested in vitro for their ability to promote megakaryocyte proliferation, differentiation and platelet formation in a co-culture system. In vitro data and epidemiological data will be compared to identify which lung cancer types are more strongly associated with megakaryocyte modulation and thrombocyctosis. Finally, the biochemical nature of the signal released by lung cancer cells affecting megakaryocyte physiology will be investigated by chromatographic fractionation, proteomics and classical biochemistry techniques. This will enable further exploration of the mechanism(s) underlying the cancer-platelet association.