Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
Sci Rep. 2019 Mar 15;9(1):4633. doi: 10.1038/s41598-019-41177-2.
While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.
虽然程序性死亡配体 1(PD-L1)、由微卫星不稳定性(MSI)引起的突变负担和 CD8+肿瘤浸润淋巴细胞(TIL)的重要性已经很明显,但 PD-L1 表达对预后的意义仍存在争议。我们评估了 PD-L1 和 MSI 或 CD8+TIL 联合标志物作为胃癌预后生物标志物的有用性。回顾性分析了 283 例胃癌患者。将>5%肿瘤细胞上的 PD-L1 表达定义为 PD-L1 阳性。PD-L1 阳性率为 15.5%(44/283)。PD-L1 阳性与侵袭性和晚期癌症显著相关,也与 MSI 显著相关,而与 CD8+TIL 无显著相关性。Kaplan-Meier 分析显示,PD-L1 阳性与预后不良显著相关(p=0.0025)。多因素分析显示,PD-L1 阳性是独立的预后不良因素(风险比[HR]:1.97,p=0.0106),与弥漫性组织学类型和淋巴结转移有关。PD-L1 与 MSI(HR:2.18)或 CD8+TIL(HR:2.57)的组合是比 PD-L1 单独预测预后的更强的因素。总之,PD-L1 和 MSI 或 CD8+TIL 的联合标志物可能是胃癌更有用的预后生物标志物,可以更好地阐明胃癌患者的免疫状态。