甲状腺乳头状癌中PSMA与NIS表达及其与¹³¹I治疗反应的关系

Expression of PSMA and NIS in Papillary Thyroid Carcinoma and Their Relationship with Response to ¹³¹I Therapy

摘要: 目的：探讨甲状腺乳头状癌(papillary thyroid carcinoma, PTC)组织中前列腺特异性膜抗原(prostate-specific membrane antigen, PSMA)与钠碘同向转运体(sodium/iodide symporter, NIS)的表达特征，分析其与¹³¹I初始治疗反应的关系，并进一步评价PSMA表达与部分侵袭性病理特征之间的相关性。方法：回顾性纳入2022年11月至2024年6月行甲状腺全切并接受¹³¹I治疗的PTC患者120例。依据《甲状腺结节和分化型甲状腺癌诊治指南(第二版)》初始治疗反应评估标准，将完全缓解和疗效不确切合并为疗效满意组(acceptable response, AR) 60例，将生化疗效不佳和结构性疗效不佳合并为疗效不满意组(incomplete response, IR) 60例。采用免疫组织化学方法检测PSMA和NIS表达，分析其与¹³¹I初始治疗反应、侵袭性病理特征及二者之间的相关性。统计学方法包括Pearson χ²检验、Spearman秩相关分析及单因素二元Logistic回归分析。结果：NIS表达水平与¹³¹I初始治疗反应显著相关，AR组中NIS中高表达更常见，而IR组中NIS低表达或无表达更常见；Logistic回归分析显示，NIS表达水平越高，与AR分组的关联越强(OR = 4.00, 95% CI: 2.30~6.97, P ≤ 0.0001)。PSMA主要定位于肿瘤相关新生血管内皮细胞，且其表达水平与¹³¹I初始治疗反应显著相关，PSMA表达每升高1个等级，归入IR组的优势增加(OR = 2.383, 95% CI: 1.454~3.907, P = 0.0006)。PSMA与NIS表达存在显著关联，并呈弱负相关趋势(Pearson χ² = 22.16, P = 0.0084; Spearman ρ = −0.196, P = 0.032)。此外，PSMA表达水平与被膜侵犯、甲状腺外侵犯及多灶性均显著相关。结论：PTC中NIS低表达和PSMA高表达均与¹³¹I初始治疗反应不佳相关，且PSMA与NIS呈弱负相关趋势。PSMA高表达还与部分侵袭性病理特征相关，提示其可能作为反映肿瘤去分化及不良生物学行为的潜在辅助标志物。

Abstract: Objective: This paper aims to investigate the expression characteristics of prostate-specific membrane antigen (PSMA) and sodium/iodide symporter (NIS) in papillary thyroid carcinoma (PTC) tissues, to analyze their relationships with the initial response to ¹³¹I therapy, and to further evaluate the association between PSMA expression and several aggressive pathological features. Methods: A total of 120 patients with PTC who underwent total thyroidectomy followed by ¹³¹I therapy between November 2022 and June 2024 were retrospectively enrolled. According to the criteria for initial therapeutic response evaluation in the Guidelines for Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Carcinoma (Second Edition), patients with excellent response and indeterminate response were grouped into the acceptable response group (AR, n = 60), whereas those with biochemical incomplete response and structural incomplete response were grouped into the incomplete response group (IR, n = 60). Immunohistochemistry was used to detect the expression of PSMA and NIS. Their associations with the initial response to ¹³¹I therapy, aggressive pathological features, and the relationship between PSMA and NIS were analyzed. Statistical analyses included Pearson’s chi-square test, Spearman’s rank correlation analysis, and univariate binary logistic regression. Results: NIS expression was significantly associated with the initial response to ¹³¹I therapy. Moderate-to-high NIS expression was more common in the AR group, whereas low or absent NIS expression was more common in the IR group. Logistic regression analysis showed that higher NIS expression was more strongly associated with the AR group (OR = 4.00, 95% CI: 2.30~6.97, P ≤ 0.0001). PSMA was mainly localized in tumor-associated neovascular endothelial cells, and its expression was significantly associated with the initial response to ¹³¹I therapy. For each one-grade increase in PSMA expression, the odds of being classified into the IR group increased (OR = 2.383, 95% CI: 1.454~3.907, P = 0.0006). PSMA expression was significantly associated with NIS expression and showed a weak negative correlation trend (Pearson χ² = 22.16, P = 0.0084; Spearman ρ = −0.196, P = 0.032). In addition, PSMA expression was significantly associated with capsular invasion, extrathyroidal extension, and multifocality. Conclusion: Low NIS expression and high PSMA expression in PTC were both associated with an unfavorable initial response to ¹³¹I therapy, and PSMA showed a weak negative correlation with NIS. High PSMA expression was also associated with several aggressive pathological features, suggesting that PSMA may serve as a potential auxiliary biomarker reflecting tumor dedifferentiation and adverse biological behavior.