Multi-omics analysis identifies DLX4 as a novel biomarker for diagnosis, prognosis, and immune infiltration: from pan-cancer to renal cancer.

Background: DLX4 is involved in the regulation of embryonic development, but its function in cancer remains unclear. Here, we conducted a pan-cancer analysis to investigate the molecular mechanisms of DLX4, with a particular emphasis on its role in renal cancer.

Methods: A comprehensive analysis of DLX4 was performed, focusing on differences in expression, prognostic value, somatic mutations, methylation modifications, and immune landscapes across various cancer types using multiple databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were utilized to explore the potential biological functions. Additionally, we evaluated the expression profile, prognostic significance, and immune infiltration of DLX4 in Kidney Renal Clear Cell Carcinoma (KIRC). The effect of DLX4 on KIRC was further validated by Spatial Transcriptomics, Real-time PCR (RT-PCR), and Immunohistochemistry experiments.

Results: DLX4 was found to be upregulated in 26 cancer types and associated with poor prognosis. It was also correlated with tumor mutational burden (TMB), microsatellite instability, mismatch repair, and methylation, and was significantly enriched in pathways related to cell proliferation. In KIRC, DLX4 expression increased along with TMB and immune scores, likely due to the infiltration of regulatory T cells (Tregs) and T-helper 2 (Th2) cells. Spatial transcriptomics revealed a strong correlation between DLX4 localization and tumor cells. Experimental validation confirmed that DLX4 expression is significantly upregulated in renal cancer tissues.

Conclusion: Our study explored the mechanisms of DLX4 in pan-cancer, especially in renal clear cell carcinoma, identifying it as a promising biomarker and therapeutic target.