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Skeletal Muscle Energy Metabolism in Women With Weight Loss and Ovarian and/or Endometrial Cancer With Weight Loss

NCT03027479CompletedNAINTERVENTIONAL

Summary

the aim is to study skeletal muscle metabolism alterations métaboliques associated with weight loss in women with ovarian and/or endometrial cancer according to BMI.

Key Facts

Lead Sponsor

University Hospital, Tours

Enrollment

Start Date

2017-03-01

Completion Date

2019-07-16

Study Type

INTERVENTIONAL

Official Title

Study of Differences in Skeletal Muscle Energy Metabolism Alterations in Women With Weight Loss and Ovarian and/or Endometrial Cancer Based on the Body Mass Index

Interventions

Samples

Conditions

Weight LossOvarian CarcinomaEndometrial Carcinoma

Eligibility

Age Range

18 Years+

Sex

FEMALE

Case group selection criteria:

Inclusion Criteria:

* Women aged 18 years old and more
* Ovarian and/or endometrial cancer
* weight loss related to cancer (weight loss \> 5% weight in one month or 10% in 6 months)
* Indication to therapeutic surgery
* Women affiliated to social security scheme
* Women who can understand French and able to sign Informed consent

Exclusion Criteria:

* Unbalanced Diabetes
* Chronic neuromuscular disorder
* Any severe uncontrolled medical condition

Control group selection criteria:

Inclusion Criteria:

* Women aged 18 years and more
* Surgery Indication for a benign endometrial and/ or ovarian disease
* Patient affiliated to social security scheme
* Women who can understand French and able to sign Informed consent

Exclusion Criteria:

* Unbalanced Diabetes
* Chronic neuromuscular disorder
* Any severe uncontrolled medical condition

Outcome Measures

Primary Outcomes

Measurement of muscle mitochondrial bioenergetics according to BMI

Measurement of muscle mitochondrial bioenergetics by high resolution oxygraphy

Time frame: muscle biopsy realized during surgery

Secondary Outcomes

on muscle biopsy

* Quantification of lipids on electron microscope * Type of muscular fibers * Analyze of gene expression and proteins involved in 1/ Mitochondrial metabolism 2/ lipid metabolism and 3/ muscular proteolysis by RTqPCR with SyBR Green and Western Blot

Time frame: muscle biopsy realized during surgery

on white adipose tissue

adipose tissue composition (fatty acids quantification, sterols, steroids) * RT-qPCR quantification of molecules involved in lipid metabolism (synthesis, transport) and in inflammation (immune profile and cytokines) * RTqPCR analysis, western blot and immunohistochemical expression of markers of transformation into brown adipose tissue * in specific milieu, in vitro experimentation on skeletal muscular cells

Time frame: adipose tissue samples taken during surgery

on ovarian cancer tumor samples

* lipid composition (fatty acids quantification, sterols, steroids) * RT-qPCR quantification of molecules involved in lipid metabolism (synthesis, transport) and in inflammation (immune profil and cytokines) * culture of tumour cells to evaluate resistance to chemotherapy (platinum)

Time frame: ovarian tumor biopsies realized during surgery

on computerized tomography

assessment of body composition (fat and muscle compartments)

Time frame: 1 day of abdominal CT scan imaging procedure performed at diagnosis

Locations

Gynecology Department, University Teaching Hospital, Tours, Tours, France

Linked Papers

2023-01-16

Total Polyunsaturated Fatty Acid Level in Abdominal Adipose Tissue as an Independent Predictor of Recurrence-Free Survival in Women with Ovarian Cancer

Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman’s ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients’ RFS was analyzed using Kaplan–Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to <0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.

Linked Investigators

Adeline Dolly

Caroline Goupille

Helene Salaun

Lobna Ouldamer

Stéphane Servais