OBJECTIVES: To investigate the relationship between the expression of S100 calcium-binding protein A4 (S100A4), high mobility group protein A1 (HMGA1) and clinicopathological features, as well as postoperative recurrence and metastasis in endometrial cancer patients. METHODS: Sixty endometrial cancer patients (observation group) were selected for this study, along with 40 patients who underwent hysterectomy for benign diseases (control group) during the same period. Surgically resected endometrial cancer tissues and normal endometrial tissues were collected. The expression levels of HMGA1 and S100A4 mRNA were detected using real-time fluorescence quantitative polymerase chain reaction (qPCR), while the HMGA1 and S100A4 protein expression was detected by immunohistochemistry and Western blot. Clinical data including tumor diameter, histological grading, distant metastasis, lymph node metastasis, depth of infiltration, lymphovascular infiltration, and International Federation of Gynecology and Obstetrics (FIGO) staging were collected. Patients with endometrial cancer were categorized into a non-recurrent-metastasis group and a recurrent-metastasis group based on their one-year postoperative follow-up results. RESULTS: The mRNA and protein expression levels of HMGA1 and S100A4 were significantly higher in endometrial cancer tissues compared to normal endometrial tissues (all P<
0.05). Protein expression of HMGA1 and S100A4 was significantly associated with tumor diameters, distant metastases, lymph node metastases, depth of infiltration and lymphovascular infiltration. Specifically, endometrial cancer patients with tumor diameters >
2 cm, distant metastases, lymph node metastases, infiltration depths beyond ½ myometrium, and higher lymphovascular infiltration rates, exhibited significantly higher positive expression of HMGA1 and S100A4 (all P<
0.05). In the recurrent-metastasis group, HMGA1 and S100A4 protein expression levels were significantly higher than those in the no recurrent-metastasis group (all P<
0.05). Significant differences were found between the two groups in terms of tumor diameter, histological grading, infiltration depth, lymphovascular infiltration and FIGO stage (all P<
0.01). Multifactorial logistic regression analysis identified HMGA1 and S100A4 protein expression, infiltration depth, lymphovascular infiltration and FIGO stage as independent risk factors for postoperative recurrence and metastasis in endometrial cancer patients after surgery. Receiver operator characteristic (ROC) curves showed that HMGA1 and S100A4 protein expression had high predictive value for postoperative recurrence and metastasis in endometrial cancer patients (all P<
0.05). CONCLUSION: The increased positive expression of HMGA1 and S100A4 in the endometrial cancer tissues is closely related to the clinicopathological features and postoperative recurrence and metastasis. HMGA1 and S100A4 have significant predictive value for assessing the likelihood of postoperative recurrence and metastasis in endometrial cancer patients.