Bioinformatics analysis and the clinical significance of TP73 in regulating the immune microenvironment and chemosensitivity of endometrial cancer

Abstract

Objective: Endometrial cancer is among the most common malignant tumors of the female reproductive system. Most patients can achieve a favorable prognosis in the early stages, but some may experience tumor progression or treatment resistance, necessitating the search for new molecular markers to improve diagnosis and treatment. TP73 plays a significant role in the development and progression of various tumors. This study aims to investigate the expression characteristics of the TP73 gene in endometrial cancer and its associations with clinicopathological parameters, patient prognosis, the immune microenvironment, and chemotherapy sensitivity. Methods: Data from the TCGA and GTEx databases were obtained from UCSC Xena. UALCAN was used to analyze the correlation between TP73 expression and clinical features. The pROC package was used to plot ROC curves to evaluate diagnostic performance. STRING was used to construct a protein‒protein interaction network, and KEGG enrichment analysis was performed using LinkedOmics. Immune infiltration analysis was conducted using CIBERSORT, GSVA, and the estimate package, while TISIDB was used to explore associations with immune molecules. CPADS and GSCA databases were used to analyze the IC50 values of chemotherapeutic drugs and identify potential targeted therapies. Results: TP73 was highly expressed in endometrial cancer tissues and significantly correlated with histological subtype, TP53 mutation status, and menopausal status (P < 0.001). The ROC curve showed an AUC of 0.895, indicating diagnostic potential. The coexpression network of TP73 was enriched primarily in pathways such as RNA transport and the proteasome. TP73 expression was positively correlated with immune cell infiltration (e.g., NK CD56bright cells) and negatively correlated with macrophages (P < 0.05) while also regulating the expression of various immune modulators. Its expression level influenced the IC50 values of chemotherapeutic agents such as cisplatin and docetaxel (P < 0.05). Conclusion: TP73 is highly expressed in endometrial cancer and has diagnostic and prognostic value. It may contribute to tumor progression by modulating the immune microenvironment and chemotherapy sensitivity, suggesting its potential as a target for precision therapy in this disease.