Adipocytokines in endometrial cancer; version 0.5
Research type
Research Study
Full title
Adipocytokines and their relationship to obesity and endometrial cancer
IRAS ID
285863
Contact name
Irene Ray
Contact email
Sponsor organisation
University of Surrey
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary
The number of women diagnosed with uterine cancer continues to rise each year. Since the early 1990s, there has been almost 55% rise in the UK. 34% of endometrial cancer can be attributed to obesity. In the obese state, the function of adipose tissue deteriorates resulting in a state of chronic inflammation. Adipocytokine-related signalling pathways promote cancer development by causing inflammation, cell proliferation, DNA damage and by inhibiting apoptosis. We postulate that adipocytokines levels are significantly different in uterine cancer patients of different weight categories and different grade/stage/ type of tumour.
Any woman attending the Royal Surrey NHS Foundation Trust with endometrial cancer will be invited to participate in the study. Consent will be sought to obtain 30mls (2 1/2 tablespoons) of venous blood at the time of surgery, on day 1 post-surgery and 3 or 6 months post-surgery during routine follow-up to check bio-marker (adiponectin, leptin, tumour necrosis factor alpha, interleukin-6, Insulin-like growth factors 1 and 2) levels to see if the markers can be used to assess response to treatment. We will also get consent to collect tissue – adipose tissue (after surgery) and uterine cancer tissue and lymph nodes (after histo-pathological evaluation) to assess for bio-markers. We will also obtain blood samples from patients undergoing chemotherapy before starting treatment and after 3rd and 6th cycles. All tissues procured will be anonymised and analysed at the oncology laboratory, Leggett building, University of Surrey and later co-related with patients’ medical data as well as with tumour grade, stage and type. We will also obtain archival anonymised tissue blocks stored at the same laboratory for analysis (previously consented for use in research).
The aim would be to calculate the levels of these six biomarkers and co-relating the levels with their BMI and tumour type/ stage/grade and assess their prognostic significance.Summary of Results
: Since the early 1990s, uterine cancer cases in the UK have increased by 55%, with obesity linked to 34% of these cases. Obesity causes chronic inflammation and insulin resistance, which can promote cancer through certain proteins and growth factors. These proteins could potentially help with diagnosing or treating endometrial cancer, but no reliable markers currently exist for these purposes.This study was designed to explore potential new markers for endometrial cancer by comparing the levels of six key biomarkers (adiponectin, leptin, IL6, TNFα, IGF1, and IGF2) in 50 patients with endometrial cancer and 50 with non-cancerous gynaecological conditions. It also looked at how these markers relate to obesity and tumour characteristics, and measured changes in marker levels six months after surgery to understand the impact of treatment.
The study found that low levels of adiponectin were associated with a 35.8% higher risk of endometrial cancer. Post-menopausal women with endometrial cancer had higher levels of IGF, while control patients had lower levels, indicating that endometrial cancer and menopause affect the IGF system. Six months after surgery, levels of adipocytokines tended to decrease whereas levels of IGF tended to increase.
Additionally, the study examined these markers in endometrial cancer tissue, fat tissue, and lymph nodes. It was found that adiponectin and leptin were more prevalent in fat tissue and lymph nodes than in cancer tissue. No direct correlation was observed between marker levels in the blood and their expression in cancer tissue, suggesting circulating marker levels were independent of their expression in endometrial tissue. The study also discovered different patterns of receptor expression in cancer versus normal tissue and noted a complex interaction involving adiponectin, cancer spread, and lymph node status, which needs further investigation.
Overall, this research offers valuable insights into potential biomarkers for endometrial cancer, how they vary between blood and tissues, and their potential clinical implications.
REC name
Wales REC 5
REC reference
21/WA/0012
Date of REC Opinion
27 Jan 2021
REC opinion
Favourable Opinion