Role of claudin-6 in high-grade endometrial carcinoma: Implications for risk stratification and personalized treatment strategies

Table 1 Summary of key findings and clinical implications of claudin-6 in high-grade endometrial carcinoma from Ebrahim et al[18]

Category	Key findings	Clinical implications
Study population and CLDN6 expression	Among 80 HGEC patients, 30% (n = 24) exhibited high CLDN6 expression (IRS ≥ 8). Strong histologic subtype association: High expression was predominantly found in aggressive subtypes like serous carcinoma (38%), carcinosarcoma (50%), and clear cell carcinoma, but was absent in high-grade endometrioid carcinoma	CLDN6 is aberrantly overexpressed in a clinically significant subset of HGEC
CLDN6 expression and pathological features	Deep myometrial invasion (≥ 50%, P = 0.038). Lymph node metastasis (P < 0.001). Lymphovascular space invasion (P = 0.024). Advanced FIGO stage (P = 0.015)	High CLDN6 expression is significantly correlated with established indicators of tumor aggressiveness
Prognostic significance	Multivariate cox regression: Disease-free survival (HR = 68.98, P = 0.022); overall survival (HR = 24.023, P = 0.038). No significant difference in Kaplan-Meier analysis	CLDN6 is an independent prognostic factor indicating high risk of recurrence and mortality
Clinical translation	Biomarker potential: Useful for risk stratification and guiding personalized treatment strategies in HGEC. Therapeutic target potential: A promising target for novel therapies like ADCs (e.g., CLDN6-23-ADC) and CAR-T. A relevant phase I clinical trial (NCT05103683) is ongoing	Offers new avenues for precision therapy, particularly in refractory HGEC cases

CLDN6: Claudin-6; HGEC: High-grade endometrial carcinoma; IRS: Immunoreactivity score; FIGO: International Federation of Gynecology and Obstetrics; HR: Hazard ratio; ADCs: Antibody-drug conjugates; CAR-T: Chimeric antigen receptor T-cell.