Identification of Clinical Relevant Molecular Subtypes of Pheochromocytoma

Pheochromocytoma (PCC) is a rare neuroendocrine tumor of the adrenal gland with a high rate of mortality if diagnosed at a late stage. Common symptoms of pheochromocytoma include headache, anxiety, palpitation, and diaphoresis. Different treatments are under observation for PCC but there is still no effective treatment option. Recently, the gene expression profiling of various tumors has provided new subtype-specific options for targeted therapies. In this study, using data sets from TCGA and the GSE19422 cohorts, we identified two distinct PCC subtypes with distinct gene expression patterns. Genes enriched in Subtype I PCCs were involved in the dopaminergic synapse, nicotine addiction, and long-term depression pathways, while genes enriched in subtype II PCCs were involved in protein digestion and absorption, vascular smooth muscle contraction, and ECM receptor interaction pathways. We further identified subtype specific genes such as ALK, IGF1R, RET, and RSPO2 for subtype I and EGFR, ESR1, and SMO for subtype II, the overexpression of which led to cell invasion and tumorigenesis. These genes identified in the present research may serve as potential subtype-specific therapeutic targets to understand the underlying mechanisms of tumorigenesis. Our findings may further guide towards the development of targeted therapies and potential molecular biomarkers against PCC.