Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, 410008, Hunan, PR China; Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410008, PR China.
Hunan Key Laboratory of Oral Health Research & Hunan 3D Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, 410008, Hunan, PR China; Department of Oral Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, 410008, PR China.
Arch Oral Biol. 2020 Nov;119:104916. doi: 10.1016/j.archoralbio.2020.104916. Epub 2020 Sep 17.
The aim of our study was to investigate the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) between oral squamous cell carcinoma (OSCC) patients with and without oral submucous fibrosis (OSF), and its correlation with clinic-pathologic features and its prognostic value.
PD-L1 and PD-1 expression was evaluated by immunohistochemical staining, double immunofluorescent staining and real-time PCR, and the correlation of PD-L1/PD-1 expression with clinical outcome was assessed.
The level of PD-L1 expression was significantly higher in OSCC with OSF than in OSCC without OSF (p = 0.006). Moreover, PD-L1 expression was strongly correlated with lymph node metastasis (p = 0.016), and advanced tumor stage (p = 0.030). Increased PD-L1 expression was positively correlated with the incidence of OSCC with OSF (p = 0.006, p = 0.008, respectively). PD-L1 expression was an independent marker of unfavorable prognosis (p = 0.035, p = 0.048, respectively). High PD-L1 expression had a significantly worse outcome in OSCC patients with OSF (p = 0.014). Double immunofluorescent staining showed that OSCC with OSF were more strongly expressed both PD-L1 and PD-1 than OSCC without OSF. Moreover, the expression of PD-L1 were upregulated in OSCC tissues than normal control (p = 0.0422), and both PD-L1 and PD-1 was significantly higher in OSCC with OSF than OSCC without OSF tissues (p = 0.0043 and, p = 0.0012, respectively).
The present study suggested that PD-L1 may be an unfavorable indicator for prognosis. PD-L1/PD-1 signaling might play an important role in the malignant transformation of OSF, and targeting PD-L1/PD-1 signaling may be a new therapeutic strategy for OSCC, especially in OSCC patients with OSF.
本研究旨在探讨口腔黏膜下纤维化(OSF)伴或不伴口腔鳞状细胞癌(OSCC)患者中程序性死亡配体-1(PD-L1)/程序性死亡-1(PD-1)的表达及其与临床病理特征的关系及其预后价值。
采用免疫组织化学染色、双重免疫荧光染色和实时 PCR 检测 PD-L1 和 PD-1 的表达,并评估 PD-L1/PD-1 表达与临床结局的相关性。
OSF 伴 OSCC 患者的 PD-L1 表达水平明显高于不伴 OSF 的 OSCC 患者(p=0.006)。此外,PD-L1 表达与淋巴结转移(p=0.016)和晚期肿瘤分期(p=0.030)密切相关。增加的 PD-L1 表达与 OSF 伴 OSCC 的发生率呈正相关(p=0.006,p=0.008)。PD-L1 表达是预后不良的独立标志物(p=0.035,p=0.048)。OSF 伴 OSCC 患者中高 PD-L1 表达的预后明显较差(p=0.014)。双重免疫荧光染色显示,与不伴 OSF 的 OSCC 相比,OSF 伴 OSCC 同时表达 PD-L1 和 PD-1 的水平更高。此外,与正常对照相比,OSCC 组织中 PD-L1 的表达上调(p=0.0422),OSF 伴 OSCC 组织中 PD-L1 和 PD-1 的表达均明显高于不伴 OSF 的 OSCC 组织(p=0.0043 和 p=0.0012)。
本研究表明,PD-L1 可能是预后不良的指标。PD-L1/PD-1 信号通路可能在 OSF 的恶性转化中发挥重要作用,针对 PD-L1/PD-1 信号通路可能是 OSCC 的一种新的治疗策略,特别是在 OSF 伴 OSCC 患者中。