1 Department of Gastroenterology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
2 Department of Gastroenterology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:2058738418790318. doi: 10.1177/2058738418790318.
Targeting of the programmed cell-death 1 ligand 1 (PD-L1) signal pathway is a promising treatment strategy in several cancers. The purpose of this study was to evaluate the clinical significance of PD-L1 in patients with colon adenocarcinoma (COAD). A total of 240 patients who were diagnosed with COAD from The Cancer Genome Atlas (TCGA) RNA-sequencing data and another cohort for pair-matched COAD samples (n = 40) in tissue microarray (TMA) were enrolled in this study. The correlation of PD-L1 or miR-191-5p expression with clinicopathological features and prognosis in patients with COAD was further analyzed using TCGA data and TMA. The Cox proportional hazard regression model was used to evaluate the association of PD-L1 or miR-191-5p expression with overall survival (OS) and tumor recurrence in patients with COAD. The microRNAs (miRNAs) that target PD-L1 gene were identified by bioinformatics and Spearman correlation analysis. We found that PD-L1 expression was increased in COAD tissues and was correlated with poor survival and tumor recurrence in patients with COAD. The increased expression of PD-L1 was attributed to the dysregulation of miR-191-5p expression rather than its genetic or epigenetic alterations. Moreover, the expression of miR-191-5p presented the negative correlation with PD-L1 expression and acted as an independent prognostic factor of OS in patients with COAD. Therefore, PD-L1 may predict poor prognosis and is negatively associated with miR-191-5p expression in patients with COAD.
靶向程序性细胞死亡配体 1(PD-L1)信号通路是几种癌症的一种有前途的治疗策略。本研究旨在评估 PD-L1 在结肠腺癌(COAD)患者中的临床意义。本研究共纳入 240 例来自癌症基因组图谱(TCGA)RNA 测序数据的 COAD 患者和另一队列中配对的 COAD 组织微阵列(TMA)样本(n=40)。使用 TCGA 数据和 TMA 进一步分析 PD-L1 或 miR-191-5p 表达与 COAD 患者临床病理特征和预后的相关性。Cox 比例风险回归模型用于评估 PD-L1 或 miR-191-5p 表达与 COAD 患者总生存(OS)和肿瘤复发的相关性。通过生物信息学和 Spearman 相关分析鉴定靶向 PD-L1 基因的 microRNAs(miRNAs)。我们发现 PD-L1 在 COAD 组织中的表达增加,与 COAD 患者的不良生存和肿瘤复发相关。PD-L1 的表达增加归因于 miR-191-5p 表达的失调,而不是其遗传或表观遗传改变。此外,miR-191-5p 的表达与 PD-L1 表达呈负相关,并且是 COAD 患者 OS 的独立预后因素。因此,PD-L1 可能预测不良预后,并且与 COAD 患者的 miR-191-5p 表达呈负相关。