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Int. J. Mol. Sci. 2016, 17(10), 1654; doi:10.3390/ijms17101654

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

1
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
2
Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
3
Joint Pituitary Research Center of Cedars-Sinai Medical Center & Peking Union Medical College Hospital, Beijing 100730, China
4
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University; Beijing 100005, China
5
Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China
6
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
7
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 13 August 2016 / Revised: 19 September 2016 / Accepted: 21 September 2016 / Published: 29 September 2016
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
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Abstract

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment. View Full-Text
Keywords: Adrenocorticotrophin (ACTH)-secreting pituitary adenoma; phenotype; genotype; osteoporosis Adrenocorticotrophin (ACTH)-secreting pituitary adenoma; phenotype; genotype; osteoporosis
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Wang, R.; Yang, Y.; Sheng, M.; Bu, D.; Huang, F.; Liu, X.; Zhou, C.; Dai, C.; Sun, B.; Zhu, J.; Qiao, Y.; Yao, Y.; Zhu, H.; Lu, L.; Pan, H.; Feng, M.; Deng, K.; Xing, B.; Lian, W.; Zhao, Y.; Jiang, C. Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis. Int. J. Mol. Sci. 2016, 17, 1654.

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