TITLE:
Research Progress and Prospects on Biomarkers for Endometrial Cancer and New Targets for Precision Diagnosis and Treatment
AUTHORS:
Guangchao Wang, Cunjian Yi
KEYWORDS:
Endometrial Carcinoma, Molecular Markers, Research Progress
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.10,
October
13,
2025
ABSTRACT: Endometrial cancer is a common malignant tumor among women in China, with 77,000 new cases and 13,500 deaths reported in 2022. Its incidence continues to rise alongside increased lifespan and lifestyle changes such as obesity and hormone exposure, exhibiting a trend toward younger age groups. Approximately 70% of patients are diagnosed at an early stage, achieving a 5-year survival rate of 95% following surgery combined with adjuvant therapy. However, 10% - 20% of cases present with distant metastasis at initial diagnosis, with a five-year survival rate below 20%. Chemotherapy resistance is prevalent, necessitating precision treatment strategies based on molecular characteristics. This review systematically summarizes the latest evidence regarding four key molecules—P53, CD146, MMR, and Claudin18.2—in the occurrence, progression, and targeted intervention of endometrial carcinoma. The TCGA classifies endometrial carcinoma into four molecular subtypes: POLE-mutant, MSI-H, low-copy-number mutation, and high-copy-number mutation. The high-copy-number mutation subtype exhibits the poorest prognosis, with p53 mutations being particularly prominent in this subtype. Wild-type p53 inhibits invasion by maintaining the epithelial phenotype and upregulating anti-EMT miRNAs, whereas mutant p53 relieves ZEB1 inhibition, promoting EMT and distant metastasis. MMR deficiency (dMMR), accounting for 20% - 30% of endometrial carcinomas, primarily arises from MLH1 promoter methylation or germline mutations, with immunohistochemical testing now standard in clinical practice. Given the high tumor mutational burden and upregulation of PD-L1 expression in dMMR tumors, immune checkpoint inhibitors (ICIs) combined with chemotherapy demonstrate significantly superior progression-free survival and overall survival compared to conventional chemotherapy. MMR status has thus emerged as a companion diagnostic marker guiding the selection of immunotherapy and targeted treatments. The adhesion molecule CD146 exhibits a high positivity rate of 63.49% in endometrial carcinoma tissues, significantly higher than in normal endometrium (5.13%). Its expression correlates positively with tumor differentiation grade, FIGO stage, and myometrial invasion depth. CD146 is widely distributed in tumor vascular endothelial cells, suggesting its involvement in cancer cell proliferation, angiogenesis, and metastasis. Claudin18.2, a tight junction protein, has emerged as a novel target for solid tumors like gastric cancer due to its high selectivity and stability. Phase II trials confirmed the safety and efficacy of its targeted drugs in advanced gastric-esophageal cancer patients. Its expression and therapeutic potential in endometrial cancer warrant further investigation. In summary, p53, CD146, MMR, and Claudin18.2 not only serve as novel biomarkers for molecular subtyping and prognostic assessment in endometrial carcinoma but also provide reliable targets for overcoming drug resistance and improving survival rates in advanced patients through targeted therapy combined with chemoradiotherapy. This suggests that personalized comprehensive treatment based on molecular characteristics will become the mainstream approach in future endometrial carcinoma management.