PD-L1和MCL-1标记物与分化型甲状腺癌预后特征的关系。
PD-L1 and MCL-1 markers and the relationship with prognostic characteristics of differentiated thyroid carcinoma.
发表日期:2023 Apr 16
作者:
Denise Engelbrecht Zantut-Wittmann, Icleia Siqueira Barreto, Ana Carolina Laus, Daniel Antunes Moreno, Camila Aparecida Moma, Frederico Fernandes Ribeiro Maia, Lígia Vera Montali da Assumpção, Rui Manuel Reis
来源:
Cellular & Molecular Immunology
摘要:
MCL-1和PD-L1蛋白与分化型甲状腺癌(DTC)的癌症机制有关。肿瘤抗原会刺激免疫细胞中PD-1的表达,PD-1结合肿瘤细胞上的PD-L1,导致免疫逃逸。MCL-1是BCL-2家族的一种抗凋亡成员,对T和B淋巴细胞的生存必不可少,并具有高度的致癌潜能。我们旨在评估MCL-1和PD-L1对DTC远期预后的临床实用性和相关性。我们包括了120名经全甲状腺切除术和放射碘治疗后至少随访2年的DTC患者。人口统计学特征、肿瘤组织病理学、持续/复发风险、与结局相关的因素、初始治疗反应、随访时的持续或无病生存率与MCL-1和PD-L1免疫组织化学表达以及BRAFV600E突变有关。其中100例(83.3%)是女性,诊断时平均年龄为46.64±16.73岁。37名(30.8%)患者属于高危、45名(37.5%)属于中危,38名(31.7%)属于低危持续/复发风险。在124.86± 65.36个月的随访结束时,48例(42.5%)仍有持续性疾病。103名(85.8%)患者患有乳头状甲状腺癌(PTC),17名(14.2%)患有滤泡状甲状腺癌(FTC)。在PTC中,中等/强PD-L1和MCL-1表达与BRAFV600E突变有关(p = 0.0467;p = 0.0044)。PD-L1还与高细胞亚型有关(p = 0.0274)。在FTC中,弱PD-L1表达与最大结节直径有关(p = 0.0100)。在TNM分期中,T2与中等强PD-L1表达相关,而T3与弱表达相关(p = 0.0490)。中等MCL-1表达与吸烟有关(p = 0.0350)。PD-L1是肿瘤细胞进展的标志物,而MCL-1是抗凋亡标志物,二者都与携带BRAFV600E突变的PTC相关,而PD-L1与更具侵袭性的PTC亚型有关。MCL-1和PD-L1可以用于组成一个评估PTC患者预后的面板。另一方面,这两个标志物对FTC患者的相关性似乎较低。版权所有©2023。Elsevier B.V.出版。
MCL-1 and PD-L1 proteins are related to carcinogenesis mechanisms in differentiated thyroid carcinoma(DTC). Tumor antigens stimulate the expression of PD-1 in immune cells, which binds to PD-L1 of tumor cells, inducing immune escape from the tumor. MCL-1, an anti-apoptotic member of the BCL-2 family, is necessary for the survival of T and B lymphocytes and has a high oncogenic potential. We aim to evaluate the clinical utility and relevance of MCL-1 and PD-L1 in the long-term prognosis of DTC.120 DTC patients after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years were included. Demographic features, tumor histopathology, persistence/recurrence risk, factors associated with outcome, initial response to therapy, persistence or disease-free at the follow-up were related to MCL-1 and PD-L1 immunohistochemical expression and BRAFV600E mutation.100(83.3%) were women, 46.64 ± 16.73 years old at diagnosis; 37(30.8%) patients were at high, 45(37.5%) of intermediate and 38(31.7%) of low disease recurrence/persistence risk. At the end of follow-up of 124.86 ± 65.36 months, 48(42.5%) had persistent disease. 103(85.8%) patients had papillary thyroid carcinoma (PTC), 17(14.2%) follicular thyroid carcinoma (FTC). In PTC, moderate/strong PD-L1 and MCL-1 expressions were associated to BRAFV600E (p=0.0467; p=0.0044). PD-L1 was also associated with tall cell subtype (p=0.0274). In FTC, weak PD-L1 expression was associated to the largest nodule diameter (p=0.0100). Strong/moderate PD-L1 expression was associated to T2 and the weak expression with T3 in TNM classification (p=0.0490). Moderate MCL-1 expression was associated to smoking (p=0.0350).PDL-1, marker of progression of tumor cells and MCL-1, anti-apoptotic marker, were associated with PTC carrying BRAFV600E mutation, while PDL-1 was associated with more aggressive PTC subtype. MCL-1 and PD-L1 could be useful in composing a panel to assess the prognosis of PTC patients. On the other hand, both markers seemed to have lower relevance to FTC patients.Copyright © 2023. Published by Elsevier B.V.