The association between psychosocial factors, angiogenesis & host Th1/Th2 immune response in patients with colorectal cancer

Alabi, Andrew

August 2013

Thesis or dissertation

© 2013 Andrew Alabi. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

Tumour angiogenesis is a critical step in the growth, metastatic spread and re-growth of colorectal cancer (CRC). VEGF-­A is one of the most studied angiogenic agents. A significant degree of the morbidity and mortality associated with colorectal cancer is related to the degree of tumour vascularity. As a consequence, considerable research has been undertaken in trying to understand the mechanisms involved in tumour associated angiogenesis and capillary permeability. A second important facet of cancer outcome is the host immune response against the tumour. The Th1/Th2 cytokine profile plays an important part in determining how the immune system operates and modulation of this has potential therapeutic value.

The efficacy of treatment for colorectal cancer is based on four primary end points: tumour response rate, disease free survival, overall survival and health related quality of life. Health related quality of life (HRQoL) is a multidimensional concept, which encompasses a patient’s perceptions of both negative and positive aspects of the four main aspects of their life: physical functioning; social well being; and disease and treatment-­related symptoms. In cancer patients, HRQoL can improve our understanding of how cancer and its therapies influence a patient’s life, and how treatment can be modified to give maximal benefit.

The aim of this study was to evaluate the impact of psychosocial factors, angiogenic cytokines (serum VEGF-­A & VEGF-­C), and Th1/Th2 cytokines (IL-­10 & IL-­12) on survival in a cohort of newly diagnosed colorectal cancer patients. The evaluation was carried out over three time points: pre-operatively, 6 weeks post-operatively and at 12 months post-­operatively. Sixty consecutive patients were assessed at the 3 time points. HRQoL was assessed using the following instruments: Hospital Anxiety and Depression Scale (HADS), Mood Rating Scale (MRS), Positive and Negative Affect Schedule (PANAS), Courtauld Emotional Control Scale (CECS), Functional Assessment of Cancer Therapy-­‐Colorectal (FACT-C), EuroQoL-­5D and Eysenck Personality Questionnaire (EPQ-­R). Quantitative ELISA was used measure serum levels of VEGF-­A, VEGF-C, IL-­10 and IL-12 in the cohort of CRC.

Patients with serum VEGF-­A levels >575pg/ml were not only significantly more likely to develop local recurrence and distant metastasis but also had poorer overall survival. Patients with advanced disease and cancer related death had significantly lower levels of post-­‐operative VEGF-­C. There was a general increase in both Th1 and Th2 cytokines in patients with CRC especially in those with advanced disease. The raised level of cytokines also correlated with poorer overall survival. A number of psychosocial factors including Pre-­operative social well being subscale of FACT-C, CECS unhappy, Higher level of education as measured on EuroQoL education, post-operative EPQ-­R neuroticism, post-­operative EPQ-­R lie and post-­operative functional well being subscale of FACT-­C were noted to be independent factors that were predictive for survival. There was a general trend of improvement in all HRQoL indices (there was a significant improvement of the emotional well being subscale of FACT-C, HADS anxiety and the negative affectivity subscale of PANAS) a year from diagnosis.

In conclusion, patients with advanced CRC had significantly higher levels of serum VEGF-­A, IL-­10 and IL­12. On the other hand, serum VEGF-­C was noted to have significantly lower levels in patients with advanced disease and low disease free survival. Pre-­operative social well being subscale of FACT-C, CECS unhappy, Higher level of education, post-operative EPQ-­R neuroticism, post-operative EPQ-­R lie and post-­operative functional well being subscale of FACT-C were noted to be independent factors predictive for survival. Having established the base-line levels of key cytokines in a cohort of CRC together with a panel of psychosocial factors the challenge now is to modify these to lead to improved patient treatment.

Postgraduate Medical Institute, The University of Hull
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