Unveiling PHF19: A Novel Prognostic Biomarker and Candidate Therapeutic Node in Pheochromocytoma and Paraganglioma

Introduction: This research endeavors to thoroughly examine the expression patterns, clinical relevance, and possible regulatory networks of PHD finger protein 19 (PHF19) in pheochromocytoma and paraganglioma (PCPG). PHF19, known for its role in tumor biology, is being investigated as a potential prognostic biomarker and immunotherapy target in PCPG. Methods: We examined RNAseq data from 184 PCPG tissues and 3 normal tissues sourced from The Cancer Genome Atlas (TCGA), as well as 84 PCPG tissues and 6 normal adrenal tissues from the GSE19422 dataset. Utilizing R software, we conducted differential expression analysis, Kaplan-Meier survival analysis, Cox regression, and gene set enrichment analysis (GSEA). Additionally, PHF19 expression in PCPG cell lines was confirmed by quantitative real-time PCR (qRT-PCR). Results: In PCPG tumor tissues, the expression of PHF19 was markedly higher than that in normal tissues (mean expression: 4.014 ± 0.044 versus 2.886 ± 0.205, p = 0.001). ROC analysis yielded an AUC of 0.940 (95% CI: 0.881–0.999), indicating PHF19's potential as a diagnostic biomarker. Elevated PHF19 expression was significantly associated with worse overall survival (OS) (HR: 9.45; 95% CI: 1.11–80.09; p = 0.039). PHF19 expression was significantly associated with multiple biological pathways, including steroid hormone biosynthesis and immune-related processes. PHF19 expression positively correlated with central memory T cell (Tcm) and effector memory T cell (Tem) infiltration, while negatively correlating with B cell infiltration and immune checkpoint genes (e.g., CD274 and SIGLEC15). Additionally, PHF19 expression correlated with sensitivity to specific chemotherapeutic agents, including vinblastine and etoposide. discussion: The results imply that PHF19 could serve as a potential prognostic indicator and immunotherapy target in PCPG. Its connection to immune cell infiltration and immune checkpoint genes points to a multifaceted role within the tumor immune microenvironment. The correlation with drug sensitivity highlights the potential for PHF19 to influence treatment outcomes. These results underscore the importance of further exploring PHF19 as a therapeutic target and biomarker in PCPG. Discussion: The results imply that PHF19 could serve as a potential prognostic indicator and immunotherapy target in PCPG. Its association with immune cell infiltration and immune checkpoint genes suggests a multifaceted role in the tumor immune microenvironment. The correlation with drug sensitivity highlights the potential for PHF19 to influence treatment outcomes. These findings underscore the importance of further investigating PHF19 as a potential immunomodulatory node and biomarker in PCPG; however, functional validation is required before any therapeutic targeting can be advocated. Conclusion: This study establishes PHF19 as a potential prognostic indicator and immunotherapy target in PCPG, highlighting its immunomodulatory potential and the need to validate its therapeutic value functionally. Subsequent studies should focus on corroborating these results in broader cohorts and on probing the therapeutic prospects of targeting PHF19 in PCPG.