Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2019

Open Access 01-12-2019 | Ovarian Cancer | Research article

A novel risk score system for assessment of ovarian cancer based on co-expression network analysis and expression level of five lncRNAs

Authors: Qian Zhao, Conghong Fan

Published in: BMC Medical Genetics | Issue 1/2019

Login to get access

Abstract

Background

Ovarian cancer (OC) is the most deadly gynaecological cancer, contributing significantly to female cancer-related deaths worldwide. Improving the outlook for OC patients depends on the identification of more reliable prognostic biomarkers for early diagnosis and survival prediction. The various roles of long non-coding RNAs (lncRNAs) in OC have attracted increasing attention. This study aimed to identify a lncRNA-based signature for survival prediction in OC patients.

Methods

RNA expression data and clinical information from a large number of OC patients were downloaded from a public database. These data were regarded as a training set to construct a weighed gene co-expression network analysis (WGCNA) network, mine stable modules, and screen differentially expressed lncRNAs. The prognostic lncRNAs were screened using univariate Cox regression analysis and the optimal prognosis lncRNA combination was screened using a Cox-PH model. The finalised lncRNA combination was used to construct the risk score system, which was validated and assessed for effectiveness using other independent datasets. Further functional pathway enrichment was performed using gene set enrichment analysis (GSEA).

Results

A co-expression network was constructed and four stable modules with OC-related biological functions were obtained. A total of 19 lncRNAs significantly related to prognosis of ovarian cancer were obtained using univariate Cox regression analysis, and the 5 prognostic signature lncRNAs GAS5, HCP5, PART1, SNHG11, and SNHG5 were used to establish a risk assessment system. The reliability of the prognostic scoring system was further confirmed using validation sets, which indicated that the risk assessment system could be used as an independent prognostic factor. Pathway enrichment analysis revealed that the network modules related to the above five prognostic genes were significantly associated with cell local adhesion, cancer signaling pathways, JAK-STAT signalling, and endogenous cell receptor interaction.

Conclusions

The risk score system established in this study could provide a novel reliable method to identify individuals at high risk of OC. In addition, the five prognostic lncRNAs identified here are promising potential prognostic biomarkers that could help to elucidate the pathogenesis of OC.
Literature
1.
2.
Yang K, Hou Y, Li A, Li ZZ, Wang WJ, Xie HY, Rong ZW, Lou G, Li K. Identification of a six-lncRNA signature associated with recurrence of ovarian cancer. Sci Rep. 2017;7(1):752.PubMedPubMedCentralCrossRef
3.
Rustin G, dBM V, Griffin C, Qian W, Swart AM. Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2010;376(9747):1155–63.PubMedCrossRef
4.
Tripathi MK, Doxtater K, Keramatnia F, Zacheaus C, Yallapu MM, Jaggi M, Chauhan SC. Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposes. Drug Discov Today. 2018;23(9):1635–43.PubMedCrossRefPubMedCentral
5.
Cheng ZP, Guo J, Chen L, Luo N, Yang WH, Qu XY. A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer. Oncotarget. 2015;6(28):25381–9.PubMedPubMedCentralCrossRef
6.
Liu R, Zeng Y, Zhou CF, Wang Y, Li X, Liu ZQ, Chen XP, Zhang W, Zhou HH. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients. Sci Rep. 2017;7(1):18.PubMedPubMedCentralCrossRef
7.
Ren CC, Li XB, Wang TZ, Wang GY, Zhao C, Liang T, Zhu YY, Li MH, Yang C, Zhao YL, et al. Functions and mechanisms of long noncoding RNAs in ovarian cancer. Int J Gynecol Cancer. 2015;25(4):566–9.PubMedCrossRef
8.
Yim GW, Kim HJ, Kim LK, Kim SW, Kim S, Nam EJ, Kim YT. Long non-coding RNA HOXA11 antisense promotes cell proliferation and invasion and predicts patient prognosis in serous ovarian cancer. Cancer Res Treat. 2017;49(3):656–68.PubMedCrossRef
9.
Zhan XH, Dong CP, Liu G, Li YX, Liu L. Panel of seven long noncoding RNA as a candidate prognostic biomarker for ovarian cancer. Onco Targets Ther. 2017;10:2805–13.PubMedPubMedCentralCrossRef
10.
Chen ZJ, Zhang Z, Xie BB, Zhang HY. Clinical significance of up-regulated lncRNA NEAT1 in prognosis of ovarian cancer. Eur Rev Med Pharmacol Sci. 2016;20(16):3373–7.PubMed
11.
Li J, Huang H, Li YG, Li L, Hou WH, You ZS. Decreased expression of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion, and indicates a poor prognosis in ovarian cancer. Oncol Rep. 2016;36(6):3241–50.PubMedCrossRef
12.
Li J, Yang C, Li YG, Chen AY, Li L, You ZS. LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation. Biosci Rep. 2017;38(2):BSR20171150.CrossRefPubMed
13.
14.
Chen JM, Cooper DN, Chuzhanova N, Férec C, Patrinos GP. Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet. 2007;8(10):762–75.PubMedCrossRef
15.
Iida M, Ikeda F, Hata J, Hirakawa Y, Ohara T, Mukai N, Yoshida D, Yonemoto K, Esaki M, Kitazono T. Development and validation of a risk assessment tool for gastric cancer in a general Japanese population. Gastric Cancer. 2018;21(3):383–90.PubMedCrossRef
16.
Pavlou M, Ambler G, Seaman SR, Guttmann O, Elliott P, King M, Omar RZ. How to develop a more accurate risk prediction model when there are few events. BMJ. 2015;351:h3868.PubMedPubMedCentralCrossRef
17.
Hung YC, Lin CL, Liu CJ, Hung H, Lin SM, Lee SD, Chen PJ, Chuang SC, Yu MW. Development of risk scoring system for stratifying population for hepatocellular carcinoma screening. Hepatology. 2015;61(6):1934–44.PubMedCrossRef
18.
Hussein AA, Ghani KR, Peabody J, Sarle R, Abaza R, Eun D, Hu J, Fumo M, Lane B, Montgomery JS, et al. Development and validation of an objective scoring tool for robot-assisted radical prostatectomy: prostatectomy assessment and competency evaluation. J Urol. 2017;197(5):1237–44.PubMedCrossRef
19.
Zhou M, Sun YY, Sun YF, Xu WY, Zhang ZY, Zhao HQ, Zhong ZH, Sun J. Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer. Oncotarget. 2016;7(22):32433–48.PubMedPubMedCentral
20.
Bolstad BM, Irizarry RA, Åstrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19(2):185–93.PubMedCrossRef
21.
Larkin MA, Blackshields G, Brown NP, Chenna R, Mcgettigan PA, Mcwilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23(21):2947–8.PubMedCrossRef
22.
Parrish RS. Effect of normalization on significance testing for oligonucleotide microarrays. J Biopharm Stat. 2004;14(3):575–89.PubMedCrossRef
23.
Ritchie ME, Phipson B, Wu D, Hu YF, Law CW, Shi W, Smyth GK. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.PubMedPubMedCentralCrossRef
24.
Zhai XF, Xue QF, Liu Q, Guo YY, Chen Z. Colon cancer recurrence-associated genes revealed by WGCNA co-expression network analysis. Mol Med Rep. 2017;16(5).PubMedPubMedCentralCrossRef
25.
26.
Tibshirani R. The lasso method for variable selection in the cox model. Stat Med. 1997;16(4):385–95.PubMedCrossRef
27.
Goeman JJ. L1 penalized estimation in the cox proportional hazards model. Biom J. 2010;52(1):70–84.PubMed
28.
Subramanian A, Tamayo P, K MV, S M, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102(43):15545–50.PubMedCrossRefPubMedCentral
29.
Chou WC, Cheng AL, Brotto M, Chuang CY. Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer. BMC Genomics. 2014;15(1):300.PubMedPubMedCentralCrossRef
30.
Liu R, Cheng Y, Yu J, Lv QL, Zhou HH. Identification and validation of gene module associated with lung cancer through coexpression network analysis. Gene. 2015;563(1):56–62.PubMedCrossRef
31.
Yang Y, Han L, Yuan Y, Li J, Hei NN, Liang H. Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types. Nat Commun. 2014;5:3231.PubMedCrossRef
32.
Adler AS, Chang HY. From description to causality: mechanisms of gene expression signatures in cancer. Cell Cycle. 2006;5(11):1148–51.PubMedCrossRef
33.
Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, et al. Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006;98(4):262–72.PubMedCrossRef
34.
Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu XS, Boyd J, Libermann TA, Cannistra SA. Gene expression signature with independent prognostic significance in epithelial ovarian cancer. J Clin Oncol. 2004;22(23):4700–10.PubMedCrossRef
35.
Zhao HJ, Ljungberg B, Grankvist K, Rasmuson T, Tibshirani R, Brooks JD. Gene expression profiling predicts survival in conventional renal cell carcinoma. PLoS Med. 2005;3(1):e13.PubMedPubMedCentralCrossRef
36.
Schneider C, King RM, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54(6):787–93.PubMedCrossRef
37.
Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.PubMedCrossRef
38.
Pickard MR, Mourtada-Maarabouni M, ., Williams GT: Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta (BBA) - Mol Basis Dis 2013, 1832(10):1613–1623.CrossRef
39.
Qiao HP, Gao WS, Huo JX, Yang ZS. Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev. 2013;14(2):1077–82.PubMedCrossRef
40.
Chen X, Guo W, Xu XJ, Su F, Wang Y, Zhang Y, Wang Q, Zhu L. Melanoma long non-coding RNA signature predicts prognostic survival and directs clinical risk-specific treatments. J Dermatol Sci. 2017;85(3):226–34.PubMedCrossRef
41.
Liang LL, Xu JC, Wang M, Xu GR, Zhang N, Wang GZ, Zhao YF. LncRNA HCP5 promotes follicular thyroid carcinoma progression via miRNAs sponge. Cell Death Dis. 2018;9(3):372.PubMedPubMedCentralCrossRef
42.
Liu N, Zhang R, Zhao XM, Jiaming SU, Bian XL, Jinsong NI, Yue Y, Cai Y, Jin JJ. A potential diagnostic marker for ovarian cancer: involvement of the histone acetyltransferase, human males absent on the first. Oncol Lett. 2013;6(2):393–400.PubMedPubMedCentralCrossRef
43.
Yu Y, Shen HM, Fang DM, Meng QJ, Xin YH. LncRNA HCP5 promotes the development of cervical cancer by regulating MACC1 via suppression of microRNA-15a. Eur Rev Med Pharmacol Sci. 2018;22(15):4812–9.PubMed
44.
Li YS, Chen J, Zhang JW, Wang ZS, Shao TT, Jiang CJ, Xu J, Li X. Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer. Oncotarget. 2015;6(28):25003–16.PubMedPubMedCentral
45.
Hu YB, Ma Z, He YM, Liu W, Su Y, Tang ZB. PART-1 functions as a competitive endogenous RNA for promoting tumor progression by sponging miR-143 in colorectal cancer. Biochem Biophys Res Commun. 2017;490(2):317–23.PubMedCrossRef
46.
Li M, Zhang WW, Zhang SJ, Wang CH, Lin YP. PART1 expression is associated with poor prognosis and tumor recurrence in stage I-III non-small cell lung cancer. J Cancer. 2017;8(10):1795–800.PubMedPubMedCentralCrossRef
47.
Sidiropoulos M, Chang A, Jung K, Diamandis EP. Expression and regulation of prostate androgen regulated transcript-1 (PART-1) and identification of differential expression in prostatic cancer. Br J Cancer. 2001;85(3):393–7.PubMedPubMedCentralCrossRef
48.
Ichigozaki Y, Fukushima S, Jinnin M, Miyashita A, Nakahara S, Tokuzumi A, Yamashita J, Kajihara I, Aoi J, Masuguchi S, et al. Serum long non-coding RNA, snoRNA host gene 5 level as a new tumor marker of malignant melanoma. Exp Dermatol. 2016;25(1):67–9.PubMedCrossRef
49.
Shi J, Xu M, Tang Q, Zhao K, Deng A, Li J. Highly sensitive determination of diclofenac based on resin beads and a novel polyclonal antibody by using flow injection chemiluminescence competitive immunoassay. Spectrochim Acta A Mol Biomol Spectrosc. 2018;191:1–7.PubMedCrossRef
50.
Shen HJ, Wang Y, Shi WD, Sun GX, Hong LJ, Zhang Y. LncRNA SNHG5/miR-26a/SOX2 signal axis enhances proliferation of chondrocyte in osteoarthritis. Acta Biochim Biophys Sin. 2018;50(2):191–8.PubMedCrossRef
51.
Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1):7–21.PubMedCrossRef
52.
53.
Li BT, Yu C, Xu Y, Liu SB, Fan HY, Pan WW. TET1 inhibits cell proliferation by inducing RASSF5 expression. Oncotarget. 2017;8(49):86395–409.PubMedPubMedCentral
54.
Seagle BL, Dandapani M, Yeh JY, Shahabi S. Wnt signaling and survival of women with high-grade serous ovarian cancer: a brief report. Int J Gynecol Cancer. 2016;26(6):1078–80.PubMedCrossRef
55.
Liu H, Zeng Z, Wang S, Li T, Mastriani E, Li QH, Bao HX, Zhou YJ, Wang X, Liu Y. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol Ther. 2017;18(12):990–9.PubMedPubMedCentralCrossRef
56.
Yoshihara K, Tsunoda T, Shigemizu D, Fujiwara H, Hatae M, Fujiwara H, Masuzaki H, Katabuchi H, Kawakami Y, Okamoto A, et al. High-risk ovarian cancer based on 126-gene expression signature is uniquely characterized by downregulation of antigen presentation pathway. Clin Cancer Res. 2012;18(5):1374–85.PubMedCrossRef
57.
Yoshihara K, Tajima A, Yahata T, Kodama S, Fujiwara H, Suzuki M, Onishi Y, Hatae M, Sueyoshi K, Fujiwara H, et al. Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets. PLoS One. 2010;5(3):e9615.PubMedPubMedCentralCrossRef
58.
Pils D, Hager G, Tong D, Aust S, Heinze G, Kohl M, Schuster E, Wolf A, Sehouli J, Braicu I, et al. Validating the impact of a molecular subtype in ovarian cancer on outcomes: a study of the OVCAD consortium. Cancer Sci. 2012;103(7):1334–41.PubMedCrossRefPubMedCentral
59.
Bonome T, Levine DA, Shih J, Randonovich M, Pise-Masison CA, Bogomolniy F, Ozbun L, Brady J, Barrett JC, Boyd J, et al. A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 2008;68(13):5478–86.PubMedCrossRefPubMedCentral
60.
Vathipadiekal V, Wang V, Wei W, Waldron L, Drapkin R, Gillette M, Skates S, Birrer M. Creation of a human Secretome: a novel composite library of human secreted proteins: validation using ovarian Cancer gene expression data and a virtual Secretome Array. Clin Cancer Res. 2015;21(21):4960–9.PubMedCrossRef
61.
Spentzos D, Levine DA, Kolia S, Otu H, Boyd J, Libermann TA, Cannistra SA. Unique gene expression profile based on pathologic response in epithelial ovarian cancer. J Clin Oncol. 2005;23(31):7911–8.PubMedCrossRef
Metadata
Title
A novel risk score system for assessment of ovarian cancer based on co-expression network analysis and expression level of five lncRNAs
Authors
Qian Zhao
Conghong Fan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-019-0832-9

Other articles of this Issue 1/2019

BMC Medical Genetics 1/2019 Go to the issue

Research article

Association of NTCP polymorphisms with clinical outcome of hepatitis B infection in Thai individuals

Research article

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

Research article

Spectrum of CFTR mutations in Chechen cystic fibrosis patients: high frequency of c.1545_1546delTA (p.Tyr515X; 1677delTA) and c.274G>A (p.Glu92Lys, E92K) mutations in North Caucasus

Case report

Isolated hypoaldosteronism as first sign of X-linked adrenal hypoplasia congenita caused by a novel mutation in NR0B1/DAX-1 gene: a case report

Research article

Cascade screening for familial hypercholesterolemia-identification of the C308Y mutation in multiple family members and relatives for the first time in mainland China

Case report

A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: a Case report