Gao Li-Min, Zhang Yue-Hua, Shi Xiaoliang, Liu Yang, Wang Junwei, Zhang Wen-Yan, Liu Wei-Ping
Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
Department of Medical Product, OrigiMed, Inc., Shanghai, China.
Front Oncol. 2022 May 10;12:821918. doi: 10.3389/fonc.2022.821918. eCollection 2022.
The clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL.
A total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients.
Univariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients ( = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 ( = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT ( = 0.001), PI3K-AKT ( = 0.02) and NF-kappa B ( < 0.001) pathways in RR patients were significantly higher than those in ET patients.
Patients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET.
复发难治性（RR）结外自然杀伤/T细胞淋巴瘤（ENKTL）的临床预后较差。有必要识别ENKTL中的RR患者并寻找新的治疗靶点，以改善RR ENKTL患者的预后。
共纳入189例具有有效临床特征的ENKTL患者。收集石蜡标本用于PD-L1表达鉴定。进行Kaplan-Meier曲线分析以进行生存分析。进行全外显子组测序（WES）以鉴定RR和有效治疗（ET）患者的突变特征。
单因素和多因素Cox比例风险回归分析显示，PD-L1表达阴性（HR = 1.132，95% CI = 0.739 - 1.734，P = 0.036）是ENKTL患者预后不良的独立预测因素。PD-L1阳性患者的总生存期（OS）显著高于PD-L1阴性患者（P = 0.009）。然后，我们将PD-L1表达作为一个危险因素添加到自然杀伤淋巴瘤预后指数（PINK）模型中，并命名为PINK+PD-L1。PINK+PD-L1模型可以显著区分RR患者、ET患者和整个队列。此外，我们的数据显示，大多数RR患者的PD-L1表达低于25%，提示RR亚型可能与PD-L1低表达有关（P = 0.019）。根据全外显子组测序（WES），我们发现RR患者中JAK-STAT（P = 0.001）、PI3K-AKT（P = 0.02）和NF-κB（P < 0.001）通路的突变频率显著高于ET患者。
当PD-L1表达低于25%时患者倾向于表现为RR。PINK+PD-L1模型可以对不同组的风险进行分层并预测ENKTL患者的OS。RR的ENKTL患者的突变谱与ET患者不同。
