Comprehensive Pan-Cancer Bioinformatics Analysis Identifies DHX58 as a Promising Therapeutic Target and Prognostic Biomarker Across Multiple Tumor Types.

BACKGROUND

DExH-box helicase 58 (DHX58/LGP2) is an innate immune regulator with a previously uncharacterized role in oncology. This study evaluates the multifaceted role of the DHX58 gene, examining its pan-cancer expression, prognostic value, and therapeutic potential across various tumor types through an extensive pan-cancer bioinformatics analysis.

METHODS

We conducted a bioinformatics analysis of DHX58 using TCGA and GTEx data from four platforms: GEPIA2, TIMER 2.0, UALCAN, and starBase. We assessed differential expression, prognostic significance and survival outcomes, drug sensitivity, functional enrichment, genomic alterations, protein-protein interactions, and DNA methylation across 32 cancer types.

RESULTS

Our findings revealed that the differential expression of the DHX58 gene across numerous cancers was context-dependent, with consistent downregulation in lung squamous cell carcinoma and upregulation in head and neck squamous cell carcinoma. Low DHX58 expression correlated with poor survival in kidney chromophobe renal cell carcinoma, sarcoma, and skin melanoma, but with favorable outcomes in other cancers, such as colon adenocarcinoma. Notably, low DHX58 expression was associated with increased sensitivity to birinapant and saracatinib. Genomic alterations were infrequent, and methylation patterns were largely unchanged. Functional enrichment analysis emphasized DHX58's established role in innate immunity and antiviral responses, with its co-expressed genes implicated in viral defense pathways. Genomic profiling identified various alterations, including mutations and copy number variations, contributing to DHX58 dysregulation. Protein-protein interaction mapping solidified its central role in immune signaling, while DNA methylation analysis highlighted epigenetic regulation as another layer of control.

CONCLUSION

Our pan-cancer analysis reveals that DHX58 has context-specific prognostic and predictive roles. While discrepancies between platforms exist, DHX58 emerges as a potential biomarker in specific cancers, particularly in the context of therapies involving agents like birinapant. These findings warrant further mechanistic and clinical investigation.