Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis.
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.
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. wangrz@126.com.|Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. wangrz@126.com.|Joint Pituitary Research Center of Cedars-Sinai Medical Center & Peking Union Medical College Hospital, Beijing 100730, China. wangrz@126.com.
Renzhi
R
Wang
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. yangyakun2004@163.com.|Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. yangyakun2004@163.com.
Yakun
Y
Yang
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. shengmm@aliyun.com.
Miaomiao
M
Sheng
Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China. dechao.bu@gmail.com.
Dechao
D
Bu
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. hfmyanyan@gmail.com.
Fengming
F
Huang
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. liuxiaohai09@126.com.|Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. liuxiaohai09@126.com.
Xiaohai
X
Liu
Joint Pituitary Research Center of Cedars-Sinai Medical Center & Peking Union Medical College Hospital, Beijing 100730, China. cuiqi.zhou@cshs.org.|Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. cuiqi.zhou@cshs.org.
Cuiqi
C
Zhou
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. daicongxinxin@163.com.|Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. daicongxinxin@163.com.
Congxin
C
Dai
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. bw_sun@163.com.|Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. bw_sun@163.com.
Bowen
B
Sun
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. zhujindong1990@sina.com.
Jindong
J
Zhu
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. qiaoyipumch@126.com.
Yi
Y
Qiao
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. yaoyongpumc@163.com.
Yong
Y
Yao
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. zhuhuijuanpumch@126.com.
Huijuan
H
Zhu
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. lulinpumch@126.com.
Lin
L
Lu
Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. panhuipumch@126.com.
Hui
H
Pan
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. fengmingpumch@126.com.
Ming
M
Feng
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. dengkanpumch@126.com.
Kan
K
Deng
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. xingbingpumch@126.com.
Bing
B
Xing
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. lianweipumch@126.com.
Wei
W
Lian
Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China. biozy@ict.ac.cn.
Yi
Y
Zhao
Center for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China. jiang@pumc.edu.cn.|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. jiang@pumc.edu.cn.
Chengyu
C
Jiang
Adrenocorticotrophin (ACTH)-secreting pituitary adenoma; genotype; osteoporosis; phenotype
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