The incidence of uterine cancer has surged by 55% in the UK since the early 1990s, with 34% of endometrial cancer cases linked to obesity. Obesity triggers chronic inflammation and insulin resistance, promoting cancer development through adipocytokines and the insulin-like growth factor (IGF) system. These factors are potential biomarkers and therapeutic targets for endometrial cancer; however, no established markers exist for screening, diagnosis, or

treatment monitoring.

This research was undertaken as an exploratory hypothesis-generating study to assess the variations in the levels of six biomarkers (adiponectin, leptin, IL6, TNFα, IGF1, and IGF2) among individuals with endometrial cancer (n=50) and those with benign gynaecological conditions (n=50). Additionally, the study aimed to explore the associations between these marker levels, obesity, and tumour characteristics. 6-months post-surgery marker levels were also measured to assess the effect of treatment. Low adiponectin indicated a 35.8% increase in endometrial cancer risk. Post-menopausal women with endometrial cancer had elevated IGF levels, opposite to control patients having reduced IGF levels, suggesting an impact of endometrial cancer and menopause on the IGF system. Adipocytokine and IGF levels showed an inverse trend six months post-surgery.

Furthermore, expressions of these markers and their receptors were evaluated in endometrial cancer tissue, fat tissue, and lymph nodes. Adiponectin and leptin demonstrated higher expression in fat tissue and lymph nodes than in endometrial cancer tissue. No correlation was found between ELISA and PCR results, suggesting circulating marker levels were independent of their expression in endometrial tissue. Adiponectin receptors, ADIPOR1 and ADIPOR2 exhibited differential expression patterns in endometrial cancer and normal endometrium, with opposite correlations to prognostic markers. Notably, a three-way interaction involving adiponectin, lympho-vascular space invasion, and lymph node cancer status was found that necessitates further revalidation for potential pathophysiological associations. This comprehensive study contributes insights into potential biomarkers, their interplay, relative abundance in blood and various tissues and their clinical implications in endometrial cancer.