The correlation between epithelial-mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma

上皮-间质转化分类与循环肿瘤细胞MMP2表达及晚期或转移性鼻咽癌预后的相关性

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Abstract

BACKGROUND: Epithelial-mesenchymal transition (EMT) and circulating tumor cells (CTCs) are key prognostic factors in nasopharyngeal carcinoma (NPC). However, the role of EMT status in CTCs for predicting outcomes in advanced NPC treated with radiotherapy after induction chemotherapy remains unclear. METHODS: A total of 143 CTC tests from 95 advanced/metastatic NPC patients were analyzed before, during, and after radiotherapy, with a 60-month follow-up. CTC count, matrix metalloproteinase 2 (MMP2)) protein expression, and EMT subtypes were examined. RESULTS: During radiotherapy, CTC counts increase but decrease afterward. Patients with higher pre-radiotherapy tumor-node-metastasis (TNM) stages have lower total and M-subtype CTC counts. Higher T and TNM stages during radiotherapy correlate with increased EMT-state CTCs, especially hybrid CTCs. EA/IgG-positive patients have a higher number of hybrid CTCs and E-type (epithelial + hybrid) CTCs, while EBV-EA-negative patients have more mesenchymal CTCs. A higher post-radiotherapy CTC count predicts relapse, and the positive rate of MMP2 expression on hybrid and epithelial CTCs is higher than that on mesenchymal CTCs. CONCLUSION: EMT status, particularly in hybrid CTCs, is a potential prognostic marker for relapse in advanced NPC after radiotherapy.

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