Abstract
Background: Heat shock protein D1 (HSPD1) is a molecular marker that is significantly highly expressed in numerous malignancies and plays a crucial role in assessing the prognostic status of patients.In the field of head and neck squamous cell carcinoma (HNSCC), the role of the HSPD1 gene in prognostic assessment and its potential link with immune cell infiltration remains largely unexplored, highlighting an urgent need for in-depth scientific research.
Methods: In this study, we analyzed the expression data of the HSPD1 gene and its accompanying clinical information from The Cancer Genome Atlas (TCGA) database. The results showed that the expression level of the HSPD1 gene was significantly upregulated in most tumours compared to normal tissues. To validate this observation, we further verified it using Human Protein Atlas data. Through multivariate Cox regression analysis, we found that HSPD1 expression was significantly correlated with several clinicopathological features, suggesting that HSPD1 has the potential to act as an independent factor influencing the survival prognosis of HNSCC patients. Accordingly, we constructed a set of nomogram to more accurately predict the impact of HSPD1 expression on the prognosis of HNSCC patients. Meanwhile, we employed various tools, such as gene ontology analysis, gene set enrichment analysis (GSEA), single-sample GSEA, and the Tumour Immunoassessment Resource database, to explore in depth the biological roles of HSPD1 in HNSCC and its association with immune cell infiltration.
Results: The mRNA and protein expression levels of HSPD1 were significantly increased in HNSCC tissues and cell lines. After Cox regression analysis, it was found that HNSCC patients with high HSPD1 expression had shorter overall survival (OS) than those with lower expression in both univariate and multivariate analyses, with statistically significant differences (p-value less than 0.05). In the assessment of the subject's work characteristics (ROC) curve, the area under the curve (AUC) of HSPD1 reached 0.846, showing high predictive accuracy.High expression of HSPD1 was strongly correlated with several clinicopathological features, including pathological N stage, histological grading, lymphovascular invasion, overall survival, and progression-free survival, and there was also a significant association with the patient's smoking history. Further functional enrichment analysis showed that HSPD1 plays an important role in tumourigenesis and cytochrome P450 metabolic pathway. Meanwhile, HSPD1 expression was positively correlated with NK CD56bright, helper T-cells (Th), and Th2 cells; and the infiltration of Mast cells, immature dendritic cells (iDC), Cytotoxic cells, Neutrophils, and mature dendritic cells (DC) was more pronounced in the low-expression group compared with the patients with high HSPD1 expression.Silencing HSPD1 reduced proliferation and migration in SCC9 and Cal27 cell lines.
Conclusion: Elevated HSPD1 expression correlates with poor prognosis in HNSCC and impacts tumor immunity. It may function as an oncogene, influencing cell proliferation and migration. The findings highlight the need for in-depth academic research to determine the exact processes and functions.