# Exploring the Impact of Obesity on Progression and Prognosis in Early-Stage Endometrioid Endometrial Carcinoma

## TL;DR

This study shows that obesity and saturated fatty acids may worsen outcomes in early-stage endometrial cancer.

## Contribution

The novel contribution is establishing a causal link between BMI and EEC prognosis using Mendelian randomization and demonstrating SFA effects on cancer cell behavior.

## Key findings

- Higher BMI is causally linked to increased risk of endometrioid endometrial carcinoma.
- Saturated fatty acids and triglycerides are associated with increased cancer progression risk.
- Palmitic acid enhances cancer cell proliferation, migration, and invasion in laboratory models.

## Abstract

Endometrioid endometrial carcinoma (EEC) is the most prevalent malignancy affecting the female reproductive system, and obesity is a significant risk factor. In this study, we examined the influence of saturated fatty acids (SFAs) on early-stage EEC progression.

A two-sample Mendelian randomization (MR) analysis using single-nucleotide polymorphisms as instrumental variables was used to assess the potential causal associations among body mass index (BMI), the main components of adipose tissue, and EEC. Clinical data from 231 patients with EEC at Benxi Central Hospital were analyzed according to BMI categories. CCK-8, apoptosis, cell cycle, scratch, and transwell assays were used to examine the biological behavior of Ishikawa cells treated with palmitic acid (PA), the main SFA component. GraphPad Prism v10.2.0 was employed to perform correlation analysis.

MR analysis revealed a statistically causal relationship between BMI and EEC (inverse variance weighted, p = 3.573 × 10−7). Furthermore, SFAs (inverse variance weighted, p = 0.032) and triglycerides (inverse variance weighted, p = 0.036) played a notable role in the influence of BMI, and a high BMI was correlated with cervical invasion risk (p < 0.001). PA promoted Ishikawa cell proliferation at 24 hours and significantly enhanced migration and invasion at 48 hours.

This research highlights the clinical significance and implications of BMI in the evaluation of poor prognosis in early-stage EEC and the potential role of SFAs in the proliferative, migratory, and invasive abilities of EEC. Our findings emphasize the importance of dietary weight management, particularly for patients with stage I EEC.