The endotheliome and the angiome in colorectal cancer

Ramcharan, Khedar Sean (2016). The endotheliome and the angiome in colorectal cancer. University of Birmingham. M.D.

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Abstract

Heterogeneous blood vessels are created by angiogenesis and vasculogenesis in colorectal cancer (CRC). Assessing endothelial activities had promising applications. However no marker has translated to clinical care. Hence a multifactorial assessment or ‘endotheliome’, including angiogenic activity, the ‘angiome’, was proposed. I tested that circulating cellular and plasma biomarkers determined outcome(s).

Flow cytometry quantified circulating endothelial cells (CECs, displaced from blood vessels) and endothelial progenitor cells (EPCs, for vasculogenesis). Plasma markers measured by ELISA were: von Willebrand factor (vWf, for endothelial damage/turnover), soluble E-selectin (adhesion in tumour migration), vascular endothelial growth factor (VEGF) and angiogenin (for the ‘angiogenic switch’). All markers were prospectively quantified in 154 CRC participants before treatment and compared to non-cancer controls. They were tested against the tumour’s histopathology and repeated after surgery +/- adjuvant therapy.

CECs and EPCs were highest in CRC and correlated to VEGF only. Angiogenin was diagnostic of CRC and vWf predicted metastasis. All markers fell after surgery but inconsistently after adjuvant treatment. Lower CD34+CD45- cells identified responders to anti-angiogenic therapy. Models incorporating CEC, EPC, angiogenin and CRC stage predicted progression within 2 years better than CRC stage alone.

In summary, the endotheliome and angiome are determinants of outcomes and may aid decisions on therapeutic strategies.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):