Identification of candidate target genes for endometrial cancer, such as ANO1, using weighted gene co‑expression network analysis

Wang,Fangzhen; Wang,Bo; Long,Junbei; Wang,Fangmin; Wu,Ping

doi:10.3892/etm.2018.6965

Identification of candidate target genes for endometrial cancer, such as ANO1, using weighted gene co‑expression network analysis

Authors:
- Fangzhen Wang
- Bo Wang
- Junbei Long
- Fangmin Wang
- Ping Wu
View Affiliations

Affiliations: The Outpatient Office, Affiliated Hospital of Xiangyang Vocational and Technical College, Xiangyang, Hubei 441000, P.R. China, Department of Gynecology, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei 430070, P.R. China, Department of Radiology, Medical School of Xiangyang Vocational and Technical College, Xiangyang, Hubei 441000, P.R. China, Department of Gynecology and Obstetrics, Zaoyang Third People's Hospital, Xiangyang, Hubei 441000, P.R. China, Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei 441000, P.R. China
Published online on: November 13, 2018 https://doi.org/10.3892/etm.2018.6965
Pages: 298-306
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Network‑based systems biology has become an important method for analysis of high‑throughput gene expression data and gene function mining. The aim of the present study was to implement a weighted gene co‑expression network analysis to screen genes that were significantly correlated with the clinical phenotype of endometrial cancer based on data from The Cancer Genome Atlas. By using the function ‘pickSoftThreshold’ in R software, the optimum soft thresholding power was determined to be 4. Subsequently, a total of 2,414 expressed genes were identified among 19,791 genes from 506 samples, which were divided into 24 modules according to the different expression patterns. After analyzing the correlation between the gene expression in these 24 modules and the clinical phenotype of endometrial cancer, the anoctamin 1 (ANO1) gene was selected for further analysis. The Chi‑squared test indicated that ANO1 was significantly associated with age (P=0.047), histological type (P<0.001), clinical stage (P<0.001), pathological grade (P<0.001) and positive peritoneal washing (P=0.001) of endometrial carcinoma. Kaplan‑Meier survival analysis revealed that a high level of ANO1 was significantly associated with a good prognosis for endometrial cancer patients. Univariate and multivariate Cox regression analysis indicated that ANO1 is an independent prognostic factor in endometrial cancer. Further characterization of the most relevant module containing ANO1 with the database for annotation, visualization and integrated discovery tool suggested that ANO1 is involved in various pathways, including metabolic pathways. The present study suggests that ANO1 may be a potential marker for good prognosis in endometrial cancer.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E and Vergote I: Endometrial cancer. Lancet. 366:491–505. 2005. View Article : Google Scholar : PubMed/NCBI
3	Berek JS: Novak's Gynecology 13th edition. Lippincott Williams & Wilkins; Philadelphia, PA, USA: 2002
4	Ueda Y, Enomoto T and Kimura T, Miyatake T, Yoshino K, Fujita M and Kimura T: Serum biomarkers for early detection of gynecologic cancers. Cancers (Basel). 2:1312–1327. 2010. View Article : Google Scholar : PubMed/NCBI
5	Roychowdhury S and Chinnaiyan AM: Translating cancer genomes and transcriptomes for precision oncology. CA Cancer J Clin. 66:75–88. 2015. View Article : Google Scholar : PubMed/NCBI
6	Langfelder P and Horvath S: WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics. 9:5592008. View Article : Google Scholar : PubMed/NCBI
7	Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O and Galietta LJ: TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science. 322:590–594. 2008. View Article : Google Scholar : PubMed/NCBI
8	Katoh M and Katoh M: FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products. Int J Oncol. 22:1375–1381. 2003.PubMed/NCBI
9	Berglund E, Akcakaya P, Berglund D, Karlsson F, Vukojevic V, Lee L, Bogdanović D, Lui WO, Larsson C, Zedenius J, et al: Functional role of the Ca²⁺-activated Cl⁻ channel DOG1/TMEM16A in gastrointestinal stromal tumor cells. Exp Cell Res. 326:315–325. 2014. View Article : Google Scholar : PubMed/NCBI
10	Rizzo FM, Palmirotta R, Marzullo A, Resta N, Cives M, Tucci M and Silvestris F: Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations. BMC Cancer. 16:872016. View Article : Google Scholar : PubMed/NCBI
11	Sauter DR, Novak I, Pedersen SF, Larsen EH and Hoffmann EK: ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Arch. 467:1495–1508. 2015. View Article : Google Scholar : PubMed/NCBI
12	Liu W, Lu M, Liu B, Huang Y and Wang K: Inhibition of Ca(2+)-activated Cl(−) channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma. Cancer Lett. 326:41–51. 2012. View Article : Google Scholar : PubMed/NCBI
13	Ruiz C, Martins JR, Rudin F, Schneider S, Dietsche T, Fischer CA, Tornillo L, Terracciano LM, Schreiber R, Bubendorf L and Kunzelmann K: Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis. PLoS One. 7:e432652012. View Article : Google Scholar : PubMed/NCBI
14	Ubby I, Bussani E, Colonna A, Stacul G, Locatelli M, Scudieri P, Galietta L and Pagani F: TMEM16A alternative splicing coordination in breast cancer. Mol Cancer. 12:752013. View Article : Google Scholar : PubMed/NCBI
15	Wu H, Guan S, Sun M, Yu Z, Zhao L, He M, Zhao H, Yao W, Wang E, Jin F, et al: Ano1/TMEM16A overexpression is associated with good prognosis in PR-positive or HER2-negative breast cancer patients following tamoxifen treatment. PLoS One. 10:e01261282015. View Article : Google Scholar : PubMed/NCBI
16	Bae JS, Park JY, Park SH, Ha SH, An AR, Noh SJ, Kwon KS, Jung SH, Park HS, Kang MJ and Jang KY: Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas. Oncotarget. 9:607–621. 2017.PubMed/NCBI
17	Jia L, Liu W, Guan L, Lu M and Wang K: Inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. PLoS One. 10:e01365842015. View Article : Google Scholar : PubMed/NCBI
18	Sui Y, Sun M, Wu F, Yang L, Di W, Zhang G, Zhong L, Ma Z, Zheng J, Fang X and Ma T: Inhibition of TMEM16A expression suppresses growth and invasion in human colorectal cancer cells. PLoS One. 9:e1154432014. View Article : Google Scholar : PubMed/NCBI
19	Hemminger J and Iwenofu OH: Discovered on gastrointestinal stromal tumours 1 (DOG1) expression in non-gastrointestinal stromal tumour (GIST) neoplasms. Histopathology. 61:170–177. 2012. View Article : Google Scholar : PubMed/NCBI
20	Lee CH, Hoang LN, Yip S, Reyes C, Marino-Enriquez A, Eilers G, Tao D, Chiang S, Fletcher JA, Soslow RA, et al: Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement. Mod Pathol. 27:751–757. 2014. View Article : Google Scholar : PubMed/NCBI
21	Camp RL, Dolled-Filhart M and Rimm DL: X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 10:7252–7259. 2004. View Article : Google Scholar : PubMed/NCBI
22	Creasman W: Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 105:1032009. View Article : Google Scholar : PubMed/NCBI
23	Shi ZZ, Shang L, Jiang YY, Hao JJ, Zhang Y, Zhang TT, Lin DC, Liu SG, Wang BS, Gong T, et al: Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization. Clin Cancer Res. 19:5867–5878. 2013. View Article : Google Scholar : PubMed/NCBI
24	Robert B, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, Zhu S, Ball CA, Nielsen TO, Patel R, et al: The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol. 165:107–113. 2004. View Article : Google Scholar : PubMed/NCBI
25	Xu B, Jin X, Min L, Li Q, Deng L, Wu H, Lin G, Chen L, Zhang H, Li C, et al: Chloride channel-3 promotes tumor metastasis by regulating membrane ruffling and is associated with poor survival. Oncotarget. 6:2434–2450. 2015.PubMed/NCBI
26	Kim TH, Kim JS, Kim ZH, Huang RB, Chae YL and Wang RS: Khz (Fusion Product of Ganoderma lucidum and Polyporus umbellatus Mycelia) induces apoptosis in human colon carcinoma HCT116 cells, accompanied by an increase in reactive oxygen species, activation of caspase 3, and increased intracellular Ca²⁺. J Med Food. 18:332–336. 2015. View Article : Google Scholar : PubMed/NCBI
27	Mazzone A, Eisenman ST, Strege PR, Yao Z, Ordog T, Gibbons SJ and Farrugia G: Inhibition of cell proliferation by a selective inhibitor of the Ca2(+)-activated Cl(−) channel, Ano1. Biochem Biophys Res Commun. 427:248–253. 2012. View Article : Google Scholar : PubMed/NCBI
28	Pontén F, Jirström K and Uhlen M: The human protein Atlas-a tool for pathology. J Pathol. 216:387–393. 2008. View Article : Google Scholar : PubMed/NCBI