Adipocytokines in Endometrial Cancer

NCT04697264 | Completed Results

• 1 other identifier: SPON/2020/012/FHMS
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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 United Kingdom (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. The investigators 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 hospital with endometrial cancer and receiving treatment here 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 3/6 months post-surgery during routine follow-up to check biomarker (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. The investigators 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 biomarkers. The investigators will also obtain blood samples from patients undergoing chemotherapy for advanced stage endometrial. All tissues procured will be anonymised and analysed at the oncology laboratory, Leggett building, University of Surrey and later correlated with patients' medical data as well as with tumour grade, stage and type. The investigators will also use archival tissue blocks stored at the same laboratory for analysis (previously consented for use in research). These are anonymised tissue and there is no link to patients' data. The aim would be to ultimately find immuno-stimulatory/ suppressive biomarkers in order to develop novel diagnostic/ prognostic tools.

Conditions

Endometrial Cancer; Obesity

Keywords

Endometrial cancer; Obesity; Adiponectin; Leptin; TNF α; IL-6; IGF 1; IGF 2

Outcome Measures

Primary Outcomes (7)

• Correlation Between Circulating Levels of These Markers and Demographic Characteristics.

  Correlation between circulating levels of these markers and demographic characteristics such as age, parity, smoking status, menopausal status, medication use, use of HRT or hormonal contraception, the prevalence of diabetes and hypertension, any prior significant medical history or history of cancer and family history of cancer.

  Data collected at baseline

• Correlation Between Circulating Levels of These Markers (Day 0) and Cancer Characteristics in the Study Population, Using Linear Regresion.

  Data on endometrial cancer histological characteristics, including grade, stage, histology, LVSI, MELF and MSI were collected from histology reports. Endometrial cancer grade is based on glandular organisation: Grade 1 (\<5% non-glandular), Grade 2 (6-50%), and Grade 3 (\>50% non-glandular). Staging reflects cancer spread, from localised to distant involvement. Type 1 (70-80%) is estrogen-related cancer usually endometrioid histology, while Type 2 (10-20%) arises from atrophic endometrium, of non-endometrioid histology. A lower grade and stage and type 1 histology is associated with better prognosis. LVSI, cancer in lymphatic/vascular spaces of the myometrium, is an independent risk factor for recurrence. MELF (microcystic, elongated, fragmented myometrial invasion) correlates with larger tumours, deeper invasion, and LVSI. MSI indicates DNA mismatch repair defects and is linked to advanced histological features, such as deep invasion and high-grade endometrial cancers.

  Data collected at baseline (day 0)

• The Difference in Circulating Plasma Levels of Adiponectin Between Study and Control Patients

  Plasma levels of adiponectin will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.

  The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.

• The Difference in Circulating Plasma Levels of Leptin, IGF1 and IGF2 Between Study and Control Patients.

  Plasma levels of leptin, IGF1 and IGF2 will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.

  The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.

• The Difference in Circulating Plasma Levels of IL6 and TNFα Between Study and Control Patients.

  Plasma levels of IL6 and TNFα will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.

  The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.

• Correlation Between the Markers and Study Patients' Obesity Status

  Correlation between the markers and patients' obesity status using WHO BMI subgroups.

  Levels of the markers were compared with BMI of the study patients at baseline i.e. Day 0

• Correlation Between the Markers and Control Patients' Obesity Status

  Correlation between the markers and patients' obesity status using WHO BMI subgroups.

  BMI was measured at baseline only for the control population.

Secondary Outcomes (8)

• Changes in Adiponectin Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).

  6 months

• Changes in Leptin, IGF1 and IGF2 Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).

  6 months

• Changes in IL6 and TNFα Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).

  6 months

• Expression of These Biomarkers and Their Receptors in Endometrial Cancer Tissue and Adipose Tissue

  The expression of these markers were investigated in the two tissue samples at baseline only (day 0).

• Expression of These Biomarkers and Their Receptors in Endometrial Cancer Tissue and Lymph Nodal Tissue

  The expression of these markers were investigated in the two tissue samples at baseline only (day 0).

Study Arms (2)

Study - Patients with endometrial cancer

Potential participants will be identified in the Royal Surrey NHS Foundation trust - either seen here or referred here and receiving her treatment here for diagnosed endometrial cancer. Patients diagnosed with endometrial cancer will be identified through the Gynaecological Oncology Multi-Disciplinary Team meeting or by the Gynaecological Oncology or Medical Oncology teams. Blood sample will be collected on the day of the surgery when they are in the theatres and then repeated on day 1 post-operative in gynaecology ward and at 3/6 months post-surgery follow-up in clinic. For the women undergoing chemotherapy, blood sample will be procured prior to commencing chemotherapy and after 3rd (with the blood test before the fourth cycle of chemotherapy) and 6th cycles of chemotherapy.

Diagnostic Test: Blood and tissue sample collection from patients

Control - patients without endometrial cancer, with benign gynaecological issues

Female patients being referred to Royal Surrey NHS foundation Trust for benign conditions (specifically not endometrial cancer) will be invited to participate as the control population.

Diagnostic Test: Blood and tissue sample collection from patients

Interventions

Blood and tissue sample collection from patients DIAGNOSTIC_TEST

Blood and tissue sample (endometrial and adipose tissue) collection from endometrial cancer patients. Blood from all control patients, endometrial sample from benign patients having surgery for benign gynaecological conditions.

Control - patients without endometrial cancer, with benign gynaecological issues; Study - Patients with endometrial cancer

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population: All patients being referred to the Royal Surrey NHS Foundation Trust with diagnosed uterine cancer will be given the research information leaflet and invited to participate as the study population of the research. Control population: Female patients being referred to Royal Surrey NHS foundation Trust for benign conditions (specifically not endometrial cancer) will be invited to participate as the control population.

You may qualify if:

• Women diagnosed with endometrial cancer
• Age 18 or above
• Of sound mind so they can give informed consent
• Historical tissue sample/ blocks from previous cases in the laboratory in the University of Surrey, also be used if appropriate consent is in place.

You may not qualify if:

• Under 18yrs age
• Unable to give consent /denies consent

Sponsors & Collaborators

• University of Surrey: lead
• Royal Surrey County Hospital NHS Foundation Trust: collaborator
• GRACE Group: collaborator

Study Sites (1)

Royal Surrey NHS Foundation Trust

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Related Publications (11)

• Cancer Research UK Uterine Cancer Statistics http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/uterine-cancer/incidence#heading-One

  BACKGROUND

• Brown KF, Rumgay H, Dunlop C, Ryan M, Quartly F, Cox A, Deas A, Elliss-Brookes L, Gavin A, Hounsome L, Huws D, Ormiston-Smith N, Shelton J, White C, Parkin DM. The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015. Br J Cancer. 2018 Apr;118(8):1130-1141. doi: 10.1038/s41416-018-0029-6. Epub 2018 Mar 23.

  PMID: 29567982 BACKGROUND

• Kyrgiou M, Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, Martin-Hirsch P, Tsilidis KK. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017 Feb 28;356:j477. doi: 10.1136/bmj.j477.

  PMID: 28246088 BACKGROUND

• Luhn P, Dallal CM, Weiss JM, Black A, Huang WY, Lacey JV Jr, Hayes RB, Stanczyk FZ, Wentzensen N, Brinton LA. Circulating adipokine levels and endometrial cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1304-12. doi: 10.1158/1055-9965.EPI-13-0258. Epub 2013 May 21.

  PMID: 23696194 BACKGROUND

• Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, Lengyel E. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011 Oct 30;17(11):1498-503. doi: 10.1038/nm.2492.

  PMID: 22037646 BACKGROUND

• Carbone F, La Rocca C, Matarese G. Immunological functions of leptin and adiponectin. Biochimie. 2012 Oct;94(10):2082-8. doi: 10.1016/j.biochi.2012.05.018. Epub 2012 Jun 26.

  PMID: 22750129 BACKGROUND

• Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park). 2002 Feb;16(2):217-26, 229; discussion 230-2.

  PMID: 11866137 BACKGROUND

• Carlson MJ, Thiel KW, Yang S, Leslie KK. Catch it before it kills: progesterone, obesity, and the prevention of endometrial cancer. Discov Med. 2012 Sep;14(76):215-22.

  PMID: 23021376 BACKGROUND

• Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J, Harris TG, Rohan TE, Xue X, Ho GY, Einstein MH, Kaplan RC, Burk RD, Wylie-Rosett J, Pollak MN, Anderson G, Howard BV, Strickler HD. A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):921-9. doi: 10.1158/1055-9965.EPI-07-2686.

  PMID: 18398032 BACKGROUND

• Dossus L, Lukanova A, Rinaldi S, Allen N, Cust AE, Becker S, Tjonneland A, Hansen L, Overvad K, Chabbert-Buffet N, Mesrine S, Clavel-Chapelon F, Teucher B, Chang-Claude J, Boeing H, Drogan D, Trichopoulou A, Benetou V, Bamia C, Palli D, Agnoli C, Galasso R, Tumino R, Sacerdote C, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, Onland-Moret NC, Redondo ML, Travier N, Sanchez MJ, Altzibar JM, Chirlaque MD, Barricarte A, Lundin E, Khaw KT, Wareham N, Fedirko V, Romieu I, Romaguera D, Norat T, Riboli E, Kaaks R. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis. Am J Epidemiol. 2013 Apr 15;177(8):787-99. doi: 10.1093/aje/kws309. Epub 2013 Mar 13.

  PMID: 23492765 BACKGROUND

• Wang T, Rohan TE, Gunter MJ, Xue X, Wactawski-Wende J, Rajpathak SN, Cushman M, Strickler HD, Kaplan RC, Wassertheil-Smoller S, Scherer PE, Ho GY. A prospective study of inflammation markers and endometrial cancer risk in postmenopausal hormone nonusers. Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):971-7. doi: 10.1158/1055-9965.EPI-10-1222. Epub 2011 Mar 17.

  PMID: 21415362 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples and tissue (endometrial and adipose)

MeSH Terms

Conditions

Endometrial Neoplasms; Obesity

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

1. Small sample size 2. The BMI of the study and the control samples were not matched 3. Control population not healthy population. Benign gynaecological conditions could influence their inflammatory marker levels, particularly in cases with endometrial issues such as abnormal uterine bleeding or endometrial hyperplasia. 4. Lack of multi-ethnicity in populations as \>90% white population. 5. Same calibrator benign endometrial sample was used as calibrator sample for all three tissue types

Results Point of Contact

• Title: Miss Irene Ray
• Organization: University of Surrey

i.ray@surrey.ac.uk

07490749704

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: January 6, 2021
• Study Start: April 12, 2021
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)