Integrated Analysis To Identify Molecular Biomarkers Of High-Grade Serous Ovarian Cancer

被引：8
作者：
Si, Manfei [1 ]
Zhang, Junji [1 ]
Cao, Jianzhong [2 ]
Xie, Zhibo [3 ]
Shu, Shan [1 ]
Zhu, Yapei [1 ]
Lang, Jinghe [1 ]
机构：
[1] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, 1 Shuaifuyuan, Beijing 100730, Peoples R China
[2] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gen Surg, Beijing, Peoples R China
[3] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Vasc Surg, Beijing, Peoples R China
来源：
ONCOTARGETS AND THERAPY | 2019年 / 12卷
关键词：
high-grade serous ovarian cancer; integrated analysis; bioinformatic analysis; differentially expressed genes; survival; biomarker; LEUCINE-ZIPPER KINASE; ENDOTHELIAL GROWTH-FACTOR; PREDICTS POOR-PROGNOSIS; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; THERAPEUTIC TARGET; TUMOR PROGRESSION; SUBUNITS; EXPRESSION; GENE;
D O I：
10.2147/OTT.S228678
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Purpose: Ovarian cancer is the leading cause of gynecologic cancer-related death worldwide. Early diagnosis of ovarian cancer can significantly improve patient prognosis. Hence, there is an urgent need to identify key diagnostic and prognostic biomarkers specific for ovarian cancer. Because high-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and accounts for the majority of deaths, we identified potential biomarkers for the early diagnosis and prognosis of HGSOC. Methods: Six datasets (GSE14001, GSE18520, GSE26712, GSE27651, GSE40595, and GSE54388) were downloaded from the Gene Expression Omnibus database for analysis. Differentially expressed genes (DEGs) between HGSOC and normal ovarian surface epithelium samples were screened via integrated analysis. Hub genes were identified by analyzing protein-protein interaction (PPI) network data. The online Kaplan-Meier plotter was utilized to evaluate the prognostic roles of these hub genes. The expression of these hub genes was confirmed with Oncomine datasets and validated by quantitative real-time PCR and Western blotting. Results: A total of 103 DEGs in patients with HGSOC-28 upregulated genes and 75 downregulated genes-were successfully screened. Enrichment analyses revealed that the upregulated genes were enriched in cell division and cell proliferation and that the downregulated genes mainly participated in the Wnt signaling pathway and various metabolic processes. Ten hub genes were associated with HGSOC pathogenesis. Seven overexpressed hub genes were partitioned into module 1 of the PPI network, which was enriched in the cell cycle and DNA replication pathways. Survival analysis revealed that MELK, CEP55 and KDR expression levels were significantly correlated with the overall survival of HGSOC patients (P < 0.05). The RNA and protein expression levels of these hub genes were validated experimentally. Conclusion: Based on an integrated analysis, we propose the further investigation of MELK, CEP55 and KDR as promising diagnostic and prognostic biomarkers of HGSOC.
引用
收藏
页码：10057 / 10075
页数：19
相关论文
共 120 条
[1]   Predicting biomarkers for ovarian cancer using gene-expression microarrays [J].
Adib, TR ;
Henderson, S ;
Perrett, C ;
Hewitt, D ;
Bourmpoulia, D ;
Ledermann, J ;
Boshoff, C .
BRITISH JOURNAL OF CANCER, 2004, 90 (03) :686-692
[2]   KDR expression is associated with the stage and cigarette smoking of the patients with lung cancer [J].
An, She-Juan ;
Nie, Qiang ;
Chen, Zhi-Hong ;
Lin, Qiu-Xiong ;
Wang, Zhen ;
Xie, Zhi ;
Chen, Shi-Liang ;
Huang, Ying ;
Zhang, Ai-Ye ;
Yan, Jin-Feng ;
Wu, Hong-Sui ;
Lin, Jia-Ying ;
Li, Rong ;
Zhang, Xu-Chao ;
Guo, Ai-Lin ;
Mok, Tony S. ;
Wu, Yi-Long .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2007, 133 (09) :635-642
[3]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[4]   An automated method for finding molecular complexes in large protein interaction networks [J].
Bader, GD ;
Hogue, CW .
BMC BIOINFORMATICS, 2003, 4 (1)
[5]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[6]   A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer [J].
Bonome, Tomas ;
Levine, Douglas A. ;
Shih, Joanna ;
Randonovich, Mike ;
Pise-Masison, Cindy A. ;
Bogomolniy, Faina ;
Ozbun, Laurent ;
Brady, John ;
Barrett, J. Carl ;
Boyd, Jeff ;
Birrer, Michael J. .
CANCER RESEARCH, 2008, 68 (13) :5478-5486
[7]   Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines [J].
Calcagno, Danielle Queiroz ;
Takeno, Sylvia Santomi ;
Gigek, Carolina Oliveira ;
Leal, Mariana Ferreira ;
Wisnieski, Fernanda ;
Chen, Elizabeth Suchi ;
Thomaz Araujo, Taissa Maira ;
Lima, Eleonidas Moura ;
Melaragno, Maria Isabel ;
Demachki, Samia ;
Assumpcao, Paulo Pimentel ;
Burbano, Rommel Rodriguez ;
Smith, Marilia Cardoso .
WORLD JOURNAL OF GASTROENTEROLOGY, 2016, 22 (43) :9506-9514
[8]   Defining NOTCH3 Target Genes in Ovarian Cancer [J].
Chen, Xu ;
Thiaville, Michelle M. ;
Chen, Li ;
Stoeck, Alexander ;
Xuan, Jianhua ;
Gao, Min ;
Shih, Ie-Ming ;
Wang, Tian-Li .
CANCER RESEARCH, 2012, 72 (09) :2294-2303
[9]   Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression [J].
Choi, Seungho ;
Ku, Ja-Lok .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 412 (02) :207-213
[10]   Relationship between epithelial cell adhesion molecule (EpCAM) overexpression and gastric cancer patients: A systematic review and meta-analysis [J].
Dai, Meng ;
Yuan, Fei ;
Fu, Cuiqun ;
Shen, Guodong ;
Hu, Shilian ;
Shen, Gan .
PLOS ONE, 2017, 12 (04)
12345678910