Oesophageal
cancer is an aggressive disease with a poor 5 year survival rate of <20% of diagnosed patients. Unfortunately, only 20-30% Oesophageal Adenocarinoma (OAC) patients show a beneficial response to
neoadjuvant therapy (neoCT).
Inflammation influences OAC given the increased risk of
cancer development and poor outcome for obese patients where altered secretion of
adipokines and
cytokines from adipose tissue contributes a pro-tumourigenic environment. We carried out a large proteomics screen of 184
proteins to compare the inflammatory and oncogenic profiles of an isogenic radioresistant in-vitro model of OAC. We found that leukaemia inhibitory factor (LIF), an
IL-6 type
cytokine, was significantly elevated in radioresistant OAC cells (p=0.007). Furthermore, significantly higher circulating levels of LIF were present in the serum from treatment-naive OAC patients who had a subsequent poor pathological response to neo-adjuvant
therapy, (p=0.037). Quantitative PCR analysis revealed expression of LIF receptor (LIFR) may function as a predictive
indicator of response to neo-adjuvant chemoradiation
therapy in OAC. LIF was demonstrated to be actively secreted from human OAC treatment-naïve biopsies and significantly correlated with the secretion of bFGF,
VEGF-A and
IL-8 (p<0.05, R=1), (p<0.05, R=0.9429), and (p<0.05, R=1) respectively. Importantly, LIF secretion negatively correlated with tumour infiltrating lymphocytes in pre-treatment OAC patient biopsies, (r=-0.8783, p=0.033). Elevated circulating LIF is a marker of poor response to neo-adjuvant treatment in OAC and secretion of this
chemokine from the tumour is tightly linked with pro-tumourigenic mediators including bFGF,
VEGF-A and
IL-8. Targeting this pathway may be a novel mechanism enhance
neoadjuvant treatment responses in OAC.