# Systemic Immune and Tumor Marker Profiles in Ovarian and Deep Infiltrating Endometriosis: Associations with Disease Severity and Symptom Burden

## TL;DR

This study identifies distinct immune and tumor marker profiles in different types of endometriosis, linking them to disease severity and symptoms.

## Contribution

The study reveals unique systemic immune and tumor marker patterns in ovarian and deep infiltrating endometriosis.

## Key findings

- OE is associated with increased monocytes and reduced neutrophils, while DIE shows elevated IL-8 and Galectin-1.
- IL-33 levels correlate with disease severity and neutrophil proportion, indicating a role in immune regulation.
- Tumor markers like CA125 and CEA correlate with disease severity and immune cell levels.

## Abstract

Endometriosis is a chronic, estrogen-dependent inflammatory disease with heterogeneous clinical manifestations and uncertain systemic immune involvement. This study aimed to characterize peripheral immune profiles and circulating tumor markers in women with ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE), and to explore their associations with disease severity, symptom burden, and physical health perception. Peripheral blood leukocyte subsets, plasma cytokines, and tumor markers (CA125, CA19-9, CEA, HE4) were analyzed in 146 patients and 50 healthy controls. OE was associated with increased monocyte counts and reduced neutrophil proportions, while DIE showed elevated levels of IL-8 and Galectin-1. IL-33 levels correlated negatively with the revised American Society for Reproductive Medicine (rASRM) scores and positively with neutrophil proportion, suggesting a role in systemic immune regulation. Tumor marker levels varied by subtype: CA19-9 was higher in OE, and CEA in DIE. CA125 correlated with disease severity, and CEA with monocyte levels. Exploratory heatmaps revealed consistent immune-tumor associations linked to anatomical severity and symptom profiles. Although exploratory, these findings highlight the presence of distinct systemic immune patterns in endometriosis and support the potential of integrative blood-based biomarkers for future diagnostic and stratification strategies.