Illini Oliver, Benej Michal, Lang-Stöberl Anna Sophie, Fabikan Hannah, Brcic Luka, Sucher Florian, Krenbek Dagmar, Krajc Tibor, Weinlinger Christoph, Hochmair Maximilian J, Valipour Arschang, Klikovits Thomas, Watzka Stefan
Department of Respiratory and Critical Care Medicine, Clinic Floridsdorf, Vienna Healthcare Group, 1130 Vienna, Austria.
Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria.
J Clin Med. 2024 Dec 2;13(23):7322. doi: 10.3390/jcm13237322.
: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype ( = 0.045). ILK intensity ( = 0.032) and positive PD-L1 ( = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival ( = 0.045, = 0.019). In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.
胸膜间皮瘤（PM）是一种预后较差的罕见癌症。预后和预测生物标志物可改善这些患者的治疗策略。程序性死亡配体1（PD-L1）、整合素连接激酶（ILK）和乳腺癌基因1相关蛋白（BAP-1）已被提出用于预测PM的预后，但现有数据有限且存在争议。这项单中心回顾性研究分析了连续诊断为PM的患者中PD-L1、ILK和BAP-1的表达模式及其预后作用的数据。在纳入的所有患者（n = 52）中，超过一半的患者PD-L1表达呈阳性（52%肿瘤比例评分（TPS）≥1%，65%综合阳性评分（CPS）≥1），69%的患者BAP-1缺失，80%的患者ILK≥50%。PD-L1阳性表达在非上皮样亚型中更常见（P = 0.045）。ILK强度（P = 0.032）和PD-L1阳性（P = 0.034）与更晚期的肿瘤分期相关。中位总生存期（OS）为16.9（95%置信区间13.1 - 25.2）个月。包括手术和早期阶段的多模式治疗（MMT）是OS更长的独立预后因素（MMT：风险比（HR）0.347，95%置信区间0.13 - 0.90，P = 0.029；晚期：HR 4.989；95%置信区间1.64 - 15.13，P = 0.005）。PD-L1 TPS≥1%或BAP-1阳性表达的患者生存数值上更差，中位OS分别为15.3（11.5；24.4）个月与20.0（11.2；34.9）个月，以及11.3（5.6；31.0）个月与20.0（15.2；28.1）个月。此外，在接受MMT的患者中，PD-L1与更差的生存相关（PD-L1 TPS≥1%：15.8（12.1 - 25.4）个月与31.3（17.4 - 95.4）个月，P = 0.053）。ILK表达≥50%不影响生存。CPS≥1%与BAP-1阳性或ILK表达≥50%的组合与更差的生存相关（P = 0.045，P = 0.019）。在这项真实世界分析中，PD-L1和BAP-1的表达与PM患者更差的生存相关。ILK无预后价值。需要更大队列的进一步研究来确定预后和预测生物标志物，以促进这种罕见癌症的个体化治疗决策优化。
