title: Molecular pathways associated with transcriptional alterations in hyperparathyroidism.
abstract: Hyperparathyroidism is characterized by the oversecretion of parathyroid hormone biochemically and increased cell proliferation histologically. Primary and secondary hyperparathyroidism exhibit distinct pathophysiology but share certain common microscopic features. The present study performed the first genome-wide expression analysis directly comparing the expression profile of primary and secondary hyperparathyroidism. Microarray gene expression analyses were performed in parathyroid tissues from 2 primary hyperparathyroidism patients and 3 secondary hyperparathyroidism patients. Unsupervised hierarchical clustering analysis identified two natural subgroups containing different types of hyperparathyroidism. Combined with additional data extracted from a publicly available database, a meta-signature was constructed to represent an intersection of two sets of differential expression profile. Multiple pathways were identified that are aberrantly regulated in hyperparathyroidism. In primary hyperparathyroidism, dysregulated pathways included cell adhesion molecules, peroxisome proliferator-activated receptor signaling pathway, and neuroactive ligand-receptor interaction. Pathways implicated in secondary hyperparathyroidism included tryptophan metabolism, tight junctions, renin-angiotensin system, steroid hormone biosynthesis, and O-glycan biosynthesis. The present study demonstrates that different pathophysiology is associated with differential gene profiling in hyperparathyroidism. Several pathways are involved in parathyroid dysregulation and may be future targets for therapeutic intervention.
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and MacKay Medical College, Taipei 10449, Taiwan, R.O.C.
authors.forename: Fang
authors.initials: F
authors.lastname: Lee
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and MacKay Medical College, Taipei 10449, Taiwan, R.O.C.; Department of Nursing, MacKay Junior College of Medicine, Nursing and Management, Tapei 11260, Taiwan, R.O.C.; Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Nursing, MacKay Junior College of Medicine, Nursing and Management, Tapei 11260, Taiwan, R.O.C.
authors.forename: Woan-Ching
authors.initials: WC
authors.lastname: Jan
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Nephrology, MacKay Memorial Hospital and Mackay Medical College, Taipei 10449, Taiwan, R.O.C.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Nephrology, MacKay Memorial Hospital and Mackay Medical College, Taipei 10449, Taiwan, R.O.C.
authors.forename: Han-Hsiang
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and MacKay Medical College, Taipei 10449, Taiwan, R.O.C.; Department of Pharmacology and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Cheng
keywords: cell adhesion; hyperparathyroidism; metabolism; pathway analysis; renin-angiotensin