title: The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma.
abstract: Currently, the diagnosis of malignant pheochromocytoma can only be made when there is clinical evidence of metastasis or extensive local invasion. Thus, there is a need for new diagnostic marker(s) to identify tumors with malignant potential. The purpose of this study was to identify microRNAs (miRNAs) that are differentially expressed between benign and malignant pheochromocytomas and assess their diagnostic accuracy. Toward this aim, we analyzed miRNA expression in benign and malignant pheochromocytoma tumor samples using whole genome microarray profiling. Microarray analysis identified eight miRNAs that were significantly differentially expressed between benign and malignant pheochromocytomas. We measured a subset of these miRNAs directly by RT-PCR and found that miR-483-5p, miR-183, and miR-101 had significantly higher expression in malignant tumors as compared to their benign counterparts. Area under the receiver operating curve (AUC) analysis indicated that miR-483-5p, miR-101, and miR-183 could be useful diagnostic markers for distinguishing malignant from benign pheochromocytomas. In addition, these miRNAs could be detected in pheochromocytoma patient serum. Overall our data suggest that misexpression of miR-483-5p, miR-101, and miR-183 is associated with malignant pheochromocytoma.
authors.affiliation: Endocrine Oncology Section, NIH/NCI/Surgery Branch, National Cancer Institute, NIH, Hatfield Clinical Research Center, Bethesda, Maryland 20892, USA.
authors.forename: E
authors.initials: E
authors.lastname: Patterson
authors.forename: R
authors.initials: R
authors.lastname: Webb
authors.forename: A
authors.initials: A
authors.lastname: Weisbrod
authors.forename: B
authors.initials: B
authors.lastname: Bian
authors.forename: M
authors.initials: M
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: A K
authors.initials: AK
authors.lastname: Holloway
authors.forename: R
authors.initials: R
authors.lastname: Krishna
authors.forename: N
authors.initials: N
authors.lastname: Nilubol
authors.forename: K
authors.initials: K
authors.lastname: Pacak
authors.forename: E
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010673:Pheochromocytoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase