Computational Analysis Of Potential Key Genes Associated With Dopamine Neurotransmission In Pheochromocytoma And Paraganglioma

Abstract

Pheochromocytoma and Paraganglioma (PCPG) are rare and potentially lethal neuroendocrine tumors. PCPG that predominantly or exclusively produce and secrete DA is rarely seen and it has been known that exclusively dopamine-secreting PCPG is related with advanced malignant features and metastases. Up to the present, little has known about the role of dopamine neurotransmission and dopaminergic system in the initiation and progression of PCPG. The genes with significant expression differences between normal tissue and pheochromocytoma and paraganglioma, survival and correlation analysis, CpG islands prediction, and miRNA-target enrichment analysis were performed by several bioinformatics tools. In the present study, it was determined that COMT gene was significantly less expressed in PCPG than in normal tissue and COMT gene showed a remarkable relationship between differential expression with shorter overall survival among the individuals with PCPG (HR=1, p=0.011). MAOA and COMT gene pair was significantly correlated with PCPG (p=0.012; R=0.19) and hsa-miR-5000-5p regulates the expression of both COMT and MAOA genes (p=0.00215, FDR=0.127). Our findings suppose that COMT may potentially be implicated in tumor suppressive mechanism. The expression values of COMT and MAOA genes, and hsa-miR-5000-5p may have the potential to be used in the genetic evaluation of the pathogenesis and prognosis of PCPG. Further in vitro and in vivo studies are required to clarify the molecular mechanism of dopaminergic system in the pathogenesis and prognosis of PCPG.

Keywords

• Dopamine
• Pheochromocytoma and Paraganglioma (PCPG)
• Dopaminergic system
• Gene expression
• Neurotransmission