Bronte Giuseppe, Puccetti Maurizio, Petracci Elisabetta, Landi Lorenza, Cravero Paola, Scodes Simona, Ulivi Paola, Ravaioli Sara, Tumedei Maria Maddalena, Burgio Marco Angelo, Cappuzzo Federico, Delmonte Angelo, Crinò Lucio, Bravaccini Sara
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Pathology Unit, Azienda Unitá Sanitaria Locale (AUSL) Imola, Imola, Italy.
Front Oncol. 2021 May 4;11:669839. doi: 10.3389/fonc.2021.669839. eCollection 2021.
Current therapy for non-small-cell lung cancer (NSCLC) frequently includes immune checkpoint inhibitors, such as pembrolizumab, and programmed death ligand 1 (PD-L1) positivity is mandatory for its use in this setting. Vimentin plays a role in carcinogenesis through the activation of the epithelial-to-mesenchymal transition (EMT) process. Its prognostic impact in NSCLC has been investigated in numerous studies but little data are available on its relation with PD-L1 expression.
We retrospectively retrieved data on patients with advanced NSCLC consecutively enrolled in a clinical trial at our institute. PD-L1 and vimentin expression were determined by immunohistochemistry. Correlations between variables were assessed using the Spearman correlation coefficient. The Kaplan-Meier method was used to estimate overall survival (OS) and the Log-rank test was used to compare survival curves. The association between demographic, clinical and biomarker information and survival was investigated with the Cox model.
Fifty-three patients were included in the study. A weak positive correlation was observed between the PD-L1 and vimentin (ρ=0.41, =0.003). Patients with PD-L1 values <1% showed a slightly better OS than those with higher values (HR=2.07; 95% CI: 0.92-4.65), but the difference was not significant (=0.080). No difference in overall survival (OS) was observed on the basis of vimentin expression (HR=1.25; 95% CI: 0.59-2.66; =0.554). Patients harboring both vimentin and PD-L1 negative expression (<1%) showed a trend towards better survival than those with ≥1% expression (HR=2.31; 95% CI: 0.87-6.17, =0.093). No significant associations were observed between gender, age at diagnosis, stage at diagnosis, histology, KRAS or EGFR status, radical surgery or immunotherapy and OS.
The weak positive association between PD-L1 and vimentin suggests a potential interplay between these biomarkers. Further research is warranted to evaluate EMT and immune escape as two components of the same process.
非小细胞肺癌（NSCLC）的当前治疗通常包括免疫检查点抑制剂，如帕博利珠单抗，并且程序性死亡配体1（PD-L1）阳性是其在此情况下使用的必要条件。波形蛋白通过激活上皮-间质转化（EMT）过程在致癌作用中发挥作用。其在NSCLC中的预后影响已在众多研究中进行了调查，但关于其与PD-L1表达关系的数据却很少。
我们回顾性检索了我院一项临床试验中连续入组的晚期NSCLC患者的数据。通过免疫组织化学法测定PD-L1和波形蛋白的表达。使用Spearman相关系数评估变量之间的相关性。采用Kaplan-Meier法估计总生存期（OS），并使用Log-rank检验比较生存曲线。使用Cox模型研究人口统计学、临床和生物标志物信息与生存之间的关联。
53例患者纳入研究。观察到PD-L1与波形蛋白之间存在弱正相关（ρ=0.41，P=0.003）。PD-L1值<1%的患者的总生存期略优于PD-L1值较高的患者（HR=2.07；95%CI：0.92-4.65），但差异无统计学意义（P=0.080）。根据波形蛋白表达情况未观察到总生存期（OS）有差异（HR=1.25；95%CI：0.59-2.66；P=0.554）。波形蛋白和PD-L1均阴性表达（<1%）的患者的生存趋势优于表达≥1%的患者（HR=2.31；95%CI：0.87-6.17，P=0.093）。在性别、诊断时年龄、诊断分期、组织学、KRAS或EGFR状态、根治性手术或免疫治疗与OS之间未观察到显著关联。
PD-L1与波形蛋白之间的弱正相关表明这些生物标志物之间可能存在相互作用。有必要进一步研究以评估EMT和免疫逃逸作为同一过程的两个组成部分。
