Evaluating HSP90AA1 as a predictive biomarker for prognosis in lung adenocarcinoma.

BACKGROUND: HSP90AA1 is a chaperone protein that plays a role in several biological processes, including inflammation and cancer. HSP90AA1 is highly expressed in lung adenocarcinoma (LUAD). However, its exact function is still unclear. This study aimed to identify HSP90AA1 as a potential biomarker for predicting prognosis in LUAD. METHODS: We used bioinformatics methods to analyze the role of HSP90AA1 in LUAD and predict its downstream pathways. Our findings clarified the role of HSP90AA1 in cellular proliferation based on a series of in vitro experiments. Additionally, we investigated its effects on the cell cycle and apoptosis using flow cytometry. RESULTS: We analyzed the expression levels of HSP90AA1 message RNA (mRNA) and protein in various normal human and tumor tissues using the The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases. Prognostic analysis of selected survival data from the TCGA database indicated that HSP90AA1 expression was associated with clinicopathological stages. The low HSP90AA1 expression group had significantly higher overall survival (OS) and disease-specific survival (DSS) rates than the high expression group. Additionally, the CancerSEA functional similarity analysis showed that HSP90AA1 was involved in several cellular functions. These included cell cycle stimulation, DNA damage response, invasion, and proliferation. Analysis of immune scores and immune cell infiltration using the ESTIMATE and TIMER databases revealed that high HSP90AA1 levels were associated with low infiltration of CD8(+) T cells and plasmacytoid dendritic cells (pDCs), while elevated infiltration of Th2 and T helper cells was also noted. Patients with high HSP90AA1 expression had lower scores in patient-derived xenografts, immune scores, and estimated scores. However, they exhibited notably higher T cell rejection rates. In vitro experiments further confirmed that HSP90AA1 knockdown significantly reduced the proliferation of H1299 cells. CONCLUSIONS: These findings show that silencing HSP90AA1 expression or using HSP90AA1 inhibitors effectively improves treatment outcomes for LUAD. Targeting HSP90AA1 could be a powerful treatment strategy for LUAD.