# HOXA5 as a Dual Modulator of Tumor Biology in Endometrial Cancer

## TL;DR

HOXA5 in endometrial cancer promotes tumor growth but also limits spread, making it a potential marker for predicting outcomes and a possible therapy target.

## Contribution

This study reveals HOXA5's dual role in endometrial cancer as both a growth promoter and a suppressor of tumor spread.

## Key findings

- High HOXA5 expression correlates with increased cell proliferation but better survival in endometrial cancer patients.
- HOXA5 is associated with reduced angiogenesis and tissue invasion markers in tumor samples.
- HOXA5 may act as a prognostic biomarker and potential therapeutic target in endometrial cancer.

## Abstract

Endometrial cancer is the most common gynecological cancer in developed countries, but predicting how it will progress remains challenging. This study focused on a gene called HOXA5, which helps control cell growth and development. We examined tissue samples from 75 patients with endometrial cancer and found that high HOXA5 expression was linked to increased tumor cell growth, but at the same time it was associated with better overall survival. Interestingly, patients with high HOXA5 levels had lower amounts of markers related to blood vessel formation and tissue invasion, which may slow down cancer’s spread. Our findings suggest that HOXA5 may act like a double-edged sword—encouraging cancer cell growth while limiting their ability to spread. This means HOXA5 could be used as a helpful marker to predict patient outcomes and might even be a future target for therapy.

Background/Objectives: Endometrial cancer (EC) is the most prevalent gynecological malignancy, with increasing incidence and mortality. HOXA5, a developmental transcription factor, has been linked to prognosis in various cancers, but its role in EC remains unclear. This study aimed to evaluate the prognostic potential of HOXA5 in EC and to explore its association with common tumor-related proteins. Methods: We analyzed 75 EC tissue samples using immunohistochemistry to evaluate HOXA5 expression and its association with clinicopathological features and tumor-related biomarkers, including Ki-67, CD31, and fibronectin. Statistical analyses included logistic regression and Kaplan–Meier survival analysis. Results: High HOXA5 expression was significantly associated with elevated Ki-67 levels (p = 0.001) but paradoxically correlated with improved overall survival (p = 0.026). CD31 and fibronectin levels were significantly lower in the high-HOXA5 group (p = 0.007 and p = 0.001, respectively), suggesting reduced angiogenic and invasive potential. However, neither marker remained significant in multivariable analysis. Conclusions: HOXA5 may exert a dual role in EC by promoting proliferation while limiting tumor progression via suppression of angiogenesis and matrix remodeling. It holds potential as a prognostic biomarker and therapeutic target.