Transcriptome Analysis Reveals Significant Differences in Gene Expression of Malignant Pheochromocytoma or Paraganglioma

Abstract

Prediction of malignant behavior of pheochromocytoma (PC) or paraganglioma (PG) is of limited value. The Cancer Genome Atlas (TCGA) and the French ‘Cortico et Médullosurrénale: les Tumeurs Endocrines’ (COMETE) network in Paris (France) facilitate accurate differentiation of malignant PC/PG based on genetic information. Therefore, the objective of this transcriptome analysis is to identify the prognostic genes underlying the differentiation of malignant PC/PG in the TCGA and COMETE databases. TCGA carries data pertaining to multigenomic analysis of 173 PC/PG surgical resection samples while the COMETE cohort contains data involving 188 PC/PG surgical resection samples. Clinical information and mRNA expression datasets were downloaded from TCGA and COMETE databases. Based on eligibility criteria, 58 of 173 PC/PG samples in TCGA and 171 of 188 PC/PG samples collected by the COMETE network were selected. Using Ingenuity Pathway Analysis, the mRNA expression of malignant and benign PC/PG was compared. The 58 samples in TCGA included 11 malignant and 47 benign cases. Among the 171 samples obtained from the COMETE cohort, 19 were malignant and 152 were benign. A comparative analysis of the mRNA expression data of the two databases revealed that 11 up/downregulated pathways involved in malignant PC/PG were related to cancer signaling, metabolic alteration, and prominent mitosis, whereas 6 upregulated genes and 1 downregulated gene were significantly enriched in the functional annotation pathways. The TCGA and COMETE databases showed differences in mRNA expression associated with malignant and benign PC/PG. Improved recognition of prognostic genes facilitates the diagnosis and treatment of PC/PG.

<p>Comprehensive Analysis of Aberrantly Expressed Competitive Endogenous RNA Network and Identification of Prognostic Biomarkers in Pheochromocytoma and Paraganglioma</p>

“…It found 11 signaling pathways that were related to metabolic alteration and cancer signaling. 13 Among these signaling pathways, dopamine signaling and cAMP signaling were also reported in our study. Another study used 183 pheochromocytoma samples and three control samples to identify differentially expressed RNAs that were annotated by conversion through the Ensembl file (Homo sapiens GRCh38.87.chr.gtf).…”

Prediction model for pheochromocytoma/paraganglioma using nCounter assay

“…Common DEGs between the metastatic group and the non‐metastatic group were found in public data, as previously described 16 . The difference of mRNA expression was reproduced in actual FFPE tissues.…”

“…Common DEGs between the metastatic group and the nonmetastatic group were found in public data, as previously described. 16 The difference of mRNA expression was reproduced in actual FFPE tissues. In high-throughput genomics, nCounter assay in FFPE tissues is known to have a relatively lower correlation than microarray or high-throughput sequencing (HTS).…”

“…A total of 35 candidate genes were selected from a previous study. 16 A well-known tumor suppressor gene TP53 was added. PDL1 and PDL2 were also added as genes related to immune checkpoint therapy.…”

Potential Biomarkers of Metastasizing Paragangliomas and Pheochromocytomas

“…On the other hand, a set of overexpressed genes could include those involved in the cell cycle, cytoskeleton regulation, Wnt signaling, c-Myc and RAS activation, and several cancer-related pathways, the deregulation of which is associated with cell survival, proliferation, growth, and motility [125,129,130]. The transcriptome analysis of the TCGA and "COrtico et MEdullosurrénale: les Tumeurs Endocrines" (COMETE) public data revealed similar significantly altered processes (cell proliferation, signaling, and metabolism) between metastasizing and benign PHEOs [131,132]. Such et al performed gene expression profiling with the view of identifying diagnostic markers for metastasizing PPGLs [130].…”