Deciphering the role of heat shock protein HSPA1L: biomarker discovery and prognostic insights in Parkinson's disease and glioma

Abstract

Background

Heat shock proteins (HSPs) play a critical role in cellular stress responses and have been implicated in numerous diseases, including Parkinson's disease (PD) and various cancers. Understanding the differential expression and functional implications of HSPs in these conditions is crucial for identifying potential therapeutic targets and biomarkers for diagnosis and prognosis.

Methods

We utilized combined datasets (GSE6613 and GSE72267) to identify and analyze the heat shock-related genes differentially expressed in PD. Gene Set Variation Analysis (GSVA) was performed to explore functional profiles, while LASSO regression was employed to screen potential PD biomarkers. In glioma, prognostic value, immune infiltration, and pathway enrichment associated with HSPA1L gene expression were assessed via Kaplan-Meier plots, ssGSEA, and enrichment analyses.

Results

In PD, we identified 17 differentially expressed HSPs. Enrichment analysis revealed significant pathways related to protein homeostasis and cellular stress responses. LASSO regression pinpointed 12 genes, including HSPA1L, as significant markers for PD, with nomogram and calibration plots indicating predictive accuracy. Stratification based on HSPA1L expression in PD highlighted differentially active biological processes, immune responses, and metabolic disruptions. In the pan-cancer analysis, HSPA1L showed variable expression across cancer types and a significant correlation with patient survival and immune infiltration. In glioma, low HSPA1L expression was associated with worse overall survival, distinct immune infiltration patterns, and altered pathway activities.

Conclusion

This integrative study reveals the substantial role of HSPs, especially HSPA1L, in the pathogenesis and prognosis of PD and glioma. Our findings offer new perspectives on the molecular mechanisms underlying these diseases and propose HSPA1L as a potential prognostic biomarker and a target for therapeutic intervention.