AHSA1 as a prognostic biomarker and potential immunotherapeutic target in HNSCC: integrative bulk RNA-seq, scRNA-seq...

Heat shock 90 kDa protein ATPase homolog 1 (AHSA1), a chaperone of heat shock protein 90 (Hsp90), is upregulated in various malignancies, where it promotes the invasion, migration, and proliferation of cancer cells. Nevertheless, the precise function of AHSA1 in head and neck squamous cell carcinoma (HNSCC) has yet to be investigated.

To comprehensively investigate AHSA1 profiles of expression in HNSCC, various techniques including bioinformatics analysis of public databases and qRT-PCR were utilized. To evaluate AHSA1's clinical significance in HNSCC, survival analysis was performed using Cox regression models and Kaplan-Meier curves. The associations between AHSA1 expression, immune microenvironment characteristics, and drug sensitivity were analyzed through bioinformatics approaches. The cellular localization and potential functions of AHSA1 in HNSCC were further investigated through single-cell RNA sequencing (scRNA-seq) analysis. Ultimately, both in vitro and in vivo experimental techniques were used to examine the biological functions of AHSA1 in HNSCC tumor growth and metastasis.

In HNSCC, AHSA1 expression was markedly upregulated and showed strong associations with clinicopathological factors such as disease stage, TP53 mutation status, and HPV infection status. Survival analysis identified AHSA1 as an independent prognostic biomarker, with elevated expression correlating with adverse clinical outcomes. Notably, an inverse relationship was observed between AHSA1 levels and tumor-infiltrating immune cell populations. Drug sensitivity analysis revealed enhanced therapeutic responsiveness to multiple chemotherapeutic agents in tumors with high AHSA1 expression. Functional validation experiments demonstrated that AHSA1 silencing suppressed tumor growth in HNSCC mice and significantly suppressed cellular proliferation, migration, and invasive potential.

In HNSCC patients, AHSA1 might be a useful biomarker for prognostic evaluation and guidance for immunotherapy. Furthermore, inhibition of AHSA1 could effectively suppress tumor growth, invasion, and migration, underscoring its potential for HNSCC treatment strategies.