Ancel Julien, Birembaut Philippe, Dewolf Maxime, Durlach Anne, Nawrocki-Raby Béatrice, Dalstein Véronique, Delepine Gonzague, Blacher Silvia, Deslée Gaëtan, Gilles Christine, Polette Myriam
Inserm, Université de Reims Champagne Ardenne, P3Cell UMR-S1250, SFR CAP-SANTE, 51097 Reims, France.
Service de pneumologie, Hôpital Maison Blanche, CHU de Reims, 51092 Reims, France.
Cancers (Basel). 2019 Sep 22;11(10):1411. doi: 10.3390/cancers11101411.
In non-metastatic non-small-cell lung cancer (NSCLC), outcomes remain poor. Adjuvant chemotherapies provide a limited improvement in disease-free survival. Recent exploratory studies on early-stage NSCLC show that immunotherapy given according to Programmed Death-Ligand 1 expression generates variable results, emphasizing a need to improve tumor characterization. We aimed to conjointly assess NSCLC, the expression of PD-L1, and epithelial-mesenchymal transition, frequently involved in tumor aggressiveness. 188 resected NSCLCs were analyzed. Among 188 patients with curatively resected NSCLC, 127 adenocarcinomas and 61 squamous cell carcinomas were stained for PD-L1 and vimentin expression. Overall survival has been compared regarding PD-L1 and vimentin statuses both separately and conjointly in Tumor Cancer Genome Atlas databases. PD-L1 and vimentin higher expressions were strongly associated ( = 4.682, < 0.0001). This co-expression occurred preferentially in tumors with lymph node invasion ( = 0.033). PD-L1 was significantly associated with high EMT features. NSCLC harboring both PD-L1/vimentin expressions were significantly associated with poor overall survival ( = 0.019). A higher co-expression of vimentin and PD-L1 was able to identify patients with worse outcomes. Similar to an important prognostic marker in NSCLC, this tandem marker needs to be further presented to anti-PD-L1 immunotherapies to improve outcome.
在非转移性非小细胞肺癌(NSCLC)中,治疗效果仍然较差。辅助化疗在无病生存期方面的改善有限。近期对早期NSCLC的探索性研究表明,根据程序性死亡配体1(PD-L1)表达进行免疫治疗产生的结果各异,这凸显了改善肿瘤特征描述的必要性。我们旨在联合评估NSCLC、PD-L1的表达以及上皮-间质转化,上皮-间质转化常与肿瘤侵袭性相关。对188例切除的NSCLC进行了分析。在188例接受根治性切除的NSCLC患者中,对127例腺癌和61例鳞状细胞癌进行了PD-L1和波形蛋白表达染色。在肿瘤癌症基因组图谱数据库中,分别并联合比较了PD-L1和波形蛋白状态下的总生存期。PD-L1和波形蛋白的高表达显著相关( = 4.682, < 0.0001)。这种共表达优先发生在有淋巴结转移的肿瘤中( = 0.033)。PD-L1与高上皮-间质转化特征显著相关。同时具有PD-L1/波形蛋白表达的NSCLC与较差的总生存期显著相关( = 0.019)。波形蛋白和PD-L1的共表达越高,越能识别出预后较差的患者。与NSCLC中的一个重要预后标志物类似,这种串联标志物需要进一步应用于抗PD-L1免疫治疗以改善预后。