Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality rates. In spite of numerous advancements have been made in therapeutic methods, the prognosis of HNSCC patients remains poor. Therefore, investigation of crucial genes during HNSCC tumorigenesis which could be exploited as biomarkers and therapeutic targets is greatly needed. In this study, original data of four independent datasets was downloaded from the Gene Expression Omnibus database and analyzed through R language to screen out differentially expressed genes. Paired like homeodomain 1 and SAM and SH3 domain-containing 1 were selected to be further explored through multiple online databases. Quantitative real-time polymerase chain reaction analysis and immunohistochemistry assay were adopted to validate the downregulation of paired like homeodomain 1 and SAM and SH3 domain-containing 1 in HNSCC and statistical analysis indicated their close associations with patient prognosis. In vitro experiments demonstrated the inhibitory effect of paired like homeodomain 1 and SAM and SH3 domain-containing 1 on HNSCC progression. Overall, we identified the aberrant downregulation of paired like homeodomain 1 and SAM and SH3 domain-containing 1 in HNSCC and suggested the potential of utilizing them as therapeutic targets or efficient biomarkers for diagnosis and prognosis evaluation. Our findings may provide novel evidences for the development of new strategies for HNSCC treatment.

头颈部鳞状细胞癌（HNSCC）是一种具有高发病率和死亡率的侵袭性恶性肿瘤。尽管治疗方法已取得许多进步，但是HNSCC患者的预后仍然很差。因此，非常需要研究HNSCC肿瘤发生过程中的关键基因，这些关键基因可以用作生物标志物和治疗靶标。在这项研究中，从Gene Expression Omnibus数据库下载了四个独立数据集的原始数据，并通过R语言进行了分析，以筛选出差异表达的基因。选择成对的homeodomain 1和包含SAM和SH3 domain的配对1，可以通过多个在线数据库进行进一步的研究。体外实验证明成对的同源域1和SAM和含SH3的域1对HNSCC的抑制作用。总体而言，我们发现HNSCC中的同源域1和SAM和含SH3域的配对配对异常下调，并提出了将其用作治疗靶标或诊断和预后评估的有效生物标志物的潜力。我们的发现可能为开发HNSCC治疗新策略提供新证据。