International College of Dentistry, Walailak University, Bangkok, Thailand.
Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Anticancer Res. 2022 May;42(5):2689-2699. doi: 10.21873/anticanres.15747.
BACKGROUND/AIM: The prognosis of advanced stage head and neck squamous cell carcinoma (HNSCC) has remained unimproved for the past decades. Therefore, novel diagnostic markers and treatment options are required. Recently, an inhibitor for immune checkpoint program death ligand-1 (PD-L1), was approved by the FDA, and used in HNSCC patients. Histatins (HTNs), one of the common antimicrobial peptides in saliva, have demonstrated wound healing and antifungal capabilities and other functions on the oral epithelium. Dysregulation of HTN1 and HTN3 has also been reported in HNSCC through genomic and proteomic studies. This study aimed to investigate the association between histatins (HTN1 and HTN3) and PD-L1 in advanced HNSCC.
Data of gene expression in HNSCC were collected from TCGA and analyzed using a data-mining platform website (https://ualcan.path.uab.edu/). Tissue microarrays containing 98 samples of HNSCC patients and non-neoplastic controls were immunolabeled against PD-L1, HTN1, and HTN3. The immunohistochemistry results were quantified using ImageJ.
The expression of PD-L1 and HTN1 was significantly higher in tumors than normal tissues (p<0.001), but no significant difference was found regarding HTN3. Metastatic HNSCC samples exhibited significantly higher expression of PD-L1 (p<0.018), compared to the non-metastatic group. Association between HTN1 and HTN3 was found using Pearson correlation coefficient (r=0.603, p<0.001). No overall survival difference was evident among our samples.
PD-L1 and HTN1 are associated with the progression of HNSCC. PD-L1 expression correlated with that of HTN3.
背景/目的:过去几十年来,晚期头颈部鳞状细胞癌(HNSCC)的预后仍未得到改善。因此,需要新的诊断标志物和治疗选择。最近,一种免疫检查点程序死亡配体-1(PD-L1)抑制剂获得了 FDA 的批准,并用于 HNSCC 患者。组织蛋白酶(HTNs)是唾液中常见的抗菌肽之一,已在口腔上皮组织中显示出愈合和抗真菌能力及其他功能。通过基因组和蛋白质组学研究,也发现 HTN1 和 HTN3 在 HNSCC 中失调。本研究旨在探讨晚期 HNSCC 中组织蛋白酶(HTN1 和 HTN3)与 PD-L1 的相关性。
从 TCGA 收集 HNSCC 患者的基因表达数据,并使用数据挖掘平台网站(https://ualcan.path.uab.edu/)进行分析。包含 98 例 HNSCC 患者和非肿瘤对照组织的组织微阵列用 PD-L1、HTN1 和 HTN3 进行免疫标记。使用 ImageJ 对免疫组化结果进行量化。
PD-L1 和 HTN1 的表达在肿瘤组织中明显高于正常组织(p<0.001),但 HTN3 没有显著差异。与非转移性组相比,转移性 HNSCC 样本中 PD-L1 的表达明显更高(p<0.018)。Pearson 相关系数(r=0.603,p<0.001)显示 HTN1 和 HTN3 之间存在关联。我们的样本中没有明显的总体生存差异。
PD-L1 和 HTN1 与 HNSCC 的进展相关。PD-L1 的表达与 HTN3 的表达相关。