PDF(Pubmed)
Abstract：
Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12-18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accurately diagnosed thyroid malignancy regardless of BRAF mutation or Hashimoto\'s thyroiditis status, overcoming genetic and autoimmune heterogeneity. A high preoperative circulating ratio predicted aggressive disease features, including lymph node metastasis, extrathyroidal extension, progression/relapse, and recurrence. Although the preoperative plasma ratio was elevated in patients with unfavorable outcomes, it had limited utility for post-surgical monitoring. In conclusion, the MMP9/miR-145 ratio is a promising biomarker in PTC that bridges genetic and immunological variabilities, enhancing preoperative diagnosis and prognostication across diverse patient subgroups. It accurately stratifies heterogenous cases by aggressiveness. The longitudinal trends indicate decreasing applicability for post-thyroidectomy surveillance. Further large-scale validation and protocol standardization can facilitate clinical translation of the MMP9/miR-145 ratio to guide personalized thyroid cancer management.
摘要：
基质金属蛋白酶9（MMP9）和microRNA-145（miR-145）已成为甲状腺癌进展和转移的重要生物标志物。然而,它们作为不同甲状腺癌亚组的统一预后指标的综合评估和临床应用仍未被探索.我们研究了MMP9/miR-145比值在甲状腺癌中的诊断和预后价值。假设它可以克服患者间的异质性,并作为一个通用的生物标志物,无论基因突变或自身免疫状态如何.分析175例成对的甲状腺乳头状癌（PTC）和正常组织中MMP9和miR-145的表达。在86名匹配的PTC患者中，围手术期和纵向评估了12-18个月的血浆水平。评估与临床病理参数和患者预后的关联。MMP9上调，miR-145在癌症组织中下调，MMP9/miR-145的中位数比对照组高17.6倍。无论BRAF突变或桥本甲状腺炎状态如何，组织比例均可准确诊断甲状腺恶性肿瘤，克服遗传和自身免疫异质性。高的术前循环比率可预测侵袭性疾病特征，包括淋巴结转移,甲状腺外延伸，进展/复发，和复发。尽管预后不良的患者术前血浆比率升高，它对术后监测的效用有限.总之,MMP9/miR-145比率是PTC中一个有前途的生物标志物，它连接了遗传和免疫学的变异性，加强不同患者亚组的术前诊断和预后。它通过侵略性准确地对异质病例进行分层。纵向趋势表明甲状腺切除术后监测的适用性下降。进一步的大规模验证和方案标准化可以促进MMP9/miR-145比率的临床翻译，以指导个性化甲状腺癌管理。
