Whole-Blood Expression of Candidate Genes Linked with Pheochromocytoma in Post-Surgery Patients: A Pilot Study

<b>Background:</b> Pheochromocytomas (PCCs) and paragangliomas (PGLs), collectively known as PPGLs, are rare neuroendocrine tumors that produce catecholamines. The majority of PPGL cases are caused by germline and/or somatic mutations in over 20 different genes. A study of post-surgical PCC patients revealed a high risk of new tumor recurrence in both hereditary and apparently sporadic cases, suggesting that some germline mutations remain undetected. Since transcript levels can indicate gene dysfunction, our study focuses on the transcriptional profiling of PCC-associated genes in post-surgical patients. <b>Methods:</b> RT-PCR was performed on blood samples from patients and a control group. The t-SNE algorithm was applied to the transcriptional data. Sanger sequencing was used to identify mutations in the coding sequences of the <i>VHL</i>, <i>SDHB</i>, <i>RET</i>, and <i>NF1</i> genes. <b>Results</b>: We obtained transcriptional profiles for 11 genes involved in the Krebs cycle and for 21 genes involved in the hypoxia, PI3K/AKT/mTOR, and RAS/RAF/ERK signaling pathways. We identified a minimal set of 16 genes with stable transcription levels that can be used to differentiate PCC patients from controls. Germline mutations in the <i>VHL</i>, <i>SDHB</i>, <i>RET</i> and <i>NF1</i> genes, which correlated with an altered transcriptional profile, were detected in three patients. <b>Conclusions</b>: Our pilot data suggest that transcript levels of the genes involved in Krebs cycle, hypoxia, PI3K/AKT/mTOR, and RAS/RAF/ERK signaling pathways indicate their potential suitability as a candidate diagnostic marker. The results from this pilot study form the basis for a larger project to investigate gene transcription in an expanded cohort of patients who have undergone surgery for PCC.