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

被引：4

作者：

Wang, Renzhi ^{[1
,2
,3
,4
]}

Yang, Yakun ^{[1
,2
]}

Sheng, Miaomiao ^{[5
,6
]}

Bu, Dechao ^{[7
]}

Huang, Fengming ^{[5
,6
]}

Liu, Xiaohai ^{[1
,2
]}

Zhou, Cuiqi ^{[4
,8
]}

Dai, Congxin ^{[1
,2
,3
]}

Sun, Bowen ^{[1
,2
]}

Zhu, Jindong ^{[5
,6
]}

Qiao, Yi ^{[1
]}

Yao, Yong ^{[1
]}

Zhu, Huijuan ^{[9
]}

Lu, Lin ^{[9
]}

Pan, Hui ^{[9
]}

Feng, Ming ^{[1
]}

Deng, Kan ^{[1
]}

Xing, Bing ^{[1
]}

Lian, Wei ^{[1
]}

Zhao, Yi ^{[7
]}

Jiang, Chengyu ^{[2
,5
,6
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Ctr Translat Med, Beijing 100730, Peoples R China

[3] Cedars Sinai Med Ctr, Joint Pituitary Res Ctr, Beijing 100730, Peoples R China

[4] Peking Union Med Coll Hosp, Beijing 100730, Peoples R China

[5] Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China

[6] Tsinghua Univ, Peking Union Med Coll, Dept Biochem & Mol Biol, Beijing 100005, Peoples R China

[7] Chinese Acad Sci, Key Lab Intelligent Informat Proc, Inst Comp Technol, Beijing 100190, Peoples R China

[8] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA

[9] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Endocrinol, Beijing 100730, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2016年 / 17卷 / 10期

基金：

中国国家自然科学基金;

关键词：

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma; phenotype; genotype; osteoporosis; CUSHINGS-SYNDROME; MECHANISMS; GENE; PATHOGENESIS; MANAGEMENT; DISEASES; TOPHAT; EXCESS; TISSUE; ALPHA;

D O I：

10.3390/ijms17101654

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha 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.

引用

页数：16

共 51 条

[1] Glucocorticoid excess during adolescence leads to a major persistent deficit in bone mass and an increase in central body fat [J].