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Journal of Cancer Research and Clinical Oncology

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06.07.2019 | Original Article – Clinical Oncology

Co-expression network analysis identified candidate biomarkers in association with progression and prognosis of breast cancer

verfasst von: Qiang Zhou, Jiangbo Ren, Jinxuan Hou, Gang Wang, Lingao Ju, Yu Xiao, Yan Gong

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2019

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Abstract

Purpose

Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. Weighted gene co-expression network analysis was used to construct free-scale gene co-expression networks and to identify potential biomarkers for breast cancer progression.

Methods

The gene expression profiles of GSE42568 were downloaded from the Gene Expression Omnibus database. RNA-sequencing data and clinical information of breast cancer from TCGA were used for validation.

Results

A total of ten modules were established by the average linkage hierarchical clustering. We identified 58 network hub genes in the significant module (R² = 0.44) and 6 hub genes (AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK), which were significantly correlated with prognosis. Receiver-operating characteristic curve validated that the mRNA levels of these six genes exhibited excellent diagnostic efficiency in the test data set of GSE42568. RNA-sequencing data from TCGA showed that the expression levels of these six genes were higher in triple-negative tumors. One-way ANOVA suggested that these six genes were upregulated at more advanced stages. The results of independent sample t test indicated that MCM10 and TTK were associated with tumor size, and that AGO2, CDC20, CDCA5, MCM10, and MYBL2 were overexpressed in lymph-node positive breast cancer.

Conclusions

AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK were identified as candidate biomarkers for further basic and clinical research on breast cancer based on co-expression analysis.

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Adams BD, Claffey KP, White BA (2009) Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Endocrinology 150:14–23. https://doi.org/10.1210/en.2008-0984 CrossRefPubMed

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. https://doi.org/10.3322/caac.21492 CrossRefPubMed

Chang IW et al (2015) CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. Am J Transl Res 7:710–722PubMedPubMedCentral

Chen T et al (2017) Role of triosephosphate isomerase and downstream functional genes on gastric cancer. Oncol Rep 38:1822–1832. https://doi.org/10.3892/or.2017.5846 CrossRefPubMed

Chen X et al (2018) A novel USP9X substrate TTK contributes to tumorigenesis in non-small-cell lung cancer. Theranostics 8:2348–2360. https://doi.org/10.7150/thno.22901 CrossRefPubMedPubMedCentral

da Huang W, Sherman BT, Lempicki RA (2009a) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13. https://doi.org/10.1093/nar/gkn923 CrossRef

da Huang W, Sherman BT, Lempicki RA (2009b) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. https://doi.org/10.1038/nprot.2008.211 CrossRef

Fan X et al (2018) B-Myb mediates proliferation and migration of non-small-cell lung cancer via suppressing IGFBP3. Int J Mol Sci. https://doi.org/10.3390/ijms19051479 CrossRefPubMedPubMedCentral

Fisher B, Land S, Mamounas E, Dignam J, Fisher ER, Wolmark N (2001) Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol 28:400–418CrossRefPubMed

Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE (1994) Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet (Lond, Engl) 343:692–695CrossRef

Gao Y, Zhang B, Wang Y, Shang G (2018) Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncol Rep 40:841–848. https://doi.org/10.3892/or.2018.6467 CrossRefPubMed

Gonzalez-Angulo AM et al (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17:1082–1089. https://doi.org/10.1158/1078-0432.Ccr-10-2560 CrossRefPubMedPubMedCentral

Guan Z, Cheng W, Huang D, Wei A (2018) High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma. Curr Res Transl Med 66:27–32. https://doi.org/10.1016/j.retram.2017.11.002 CrossRefPubMed

Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z (2010) An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res Treat 123:725–731. https://doi.org/10.1007/s10549-009-0674-9 CrossRefPubMed

Jung KH et al (2018) Adjuvant subcutaneous trastuzumab for HER2-positive early breast cancer: subgroup analyses of safety and active medical conditions by body weight in the SafeHer phase III study. The oncologist 23:1137–1143. https://doi.org/10.1634/theoncologist.2018-0065 CrossRefPubMedPubMedCentral

Kang G et al (2013) Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer. PloS One 8:e82770. https://doi.org/10.1371/journal.pone.0082770 CrossRefPubMedPubMedCentral

Khalil MY, Grandis JR, Shin DM (2003) Targeting epidermal growth factor receptor: novel therapeutics in the management of cancer. Expert Rev Anticancer Ther 3:367–380. https://doi.org/10.1586/14737140.3.3.367 CrossRefPubMed

King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science (New York) 229:974–976CrossRef

Landi MT et al (2008) Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival. PloS One 3:e1651. https://doi.org/10.1371/journal.pone.0001651 CrossRefPubMedPubMedCentral

Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinform 9:559. https://doi.org/10.1186/1471-2105-9-559 CrossRef

Li WM et al (2016) MCM10 overexpression implicates adverse prognosis in urothelial carcinoma. Oncotarget 7:77777–77792. https://doi.org/10.18632/oncotarget.12795 CrossRefPubMedPubMedCentral

Lin D et al (1994) Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. Proc Natl Acad Sci USA 91:10079–10083CrossRefPubMed

Lu P et al (2014) Genome-wide gene expression profile analyses identify CTTN as a potential prognostic marker in esophageal cancer. PloS One 9:e88918. https://doi.org/10.1371/journal.pone.0088918 CrossRefPubMedPubMedCentral

Mahadevappa R et al (2018) DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer. Cancers. https://doi.org/10.3390/cancers10090282 CrossRefPubMedPubMedCentral

Mannefeld M, Klassen E, Gaubatz S (2009) B-MYB is required for recovery from the DNA damage-induced G2 checkpoint in p53 mutant cells. Cancer Res 69:4073–4080. https://doi.org/10.1158/0008-5472.can-08-4156 CrossRefPubMed

Musa J, Aynaud MM, Mirabeau O, Delattre O, Grunewald TG (2017) MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis. Cell Death Dis 8:e2895. https://doi.org/10.1038/cddis.2017.244 CrossRefPubMedPubMedCentral

O’Shaughnessy J (2005) Extending survival with chemotherapy in metastatic breast cancer. Oncologist 10(Suppl 3):20–29. https://doi.org/10.1634/theoncologist.10-90003-20 CrossRefPubMed

Paterson MC et al (1991) Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer. Cancer Res 51:556–567PubMed

Paul D, Ghorai S, Dinesh US, Shetty P, Chattopadhyay S, Santra MK (2017) Cdc20 directs proteasome-mediated degradation of the tumor suppressor SMAR1 in higher grades of cancer through the anaphase promoting complex. Cell Death Dis 8:e2882. https://doi.org/10.1038/cddis.2017.270 CrossRefPubMedPubMedCentral

Peng YP et al (2016) The expression and prognostic roles of MCMs in pancreatic cancer. PloS One 11:e0164150. https://doi.org/10.1371/journal.pone.0164150 CrossRefPubMedPubMedCentral

Press MF et al (1997) HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15:2894–2904. https://doi.org/10.1200/jco.1997.15.8.2894 CrossRefPubMed

Redig AJ, McAllister SS (2013) Breast cancer as a systemic disease: a view of metastasis. J Intern Med 274:113–126. https://doi.org/10.1111/joim.12084 CrossRefPubMedPubMedCentral

Ren F et al (2015) MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer. Am J Cancer Res 5:1542–1552PubMedPubMedCentral

Rimawi M et al (2018) First-line trastuzumab plus an aromatase inhibitor, with or without pertuzumab, in human epidermal growth factor receptor 2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (PERTAIN): a randomized open-label phase II trial. J Clin Oncol 36:2826–2835. https://doi.org/10.1200/jco.2017.76.7863 CrossRefPubMed

Sagara Y et al (2018) Effectiveness of neo-adjuvant systemic therapy with trastuzumab for basal HER2 type breast cancer: results from retrospective cohort study of Japan Breast Cancer Research Group (JBCRG)-C03. Breast Cancer Res Treat 171:675–683. https://doi.org/10.1007/s10549-018-4873-0 CrossRefPubMed

Sala A (2005) B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer. Eur J Cancer (Oxford, England: 1990) 41:2479–2484. https://doi.org/10.1016/j.ejca.2005.08.004 CrossRef

Shen Z et al (2018) CDCA5 regulates proliferation in hepatocellular carcinoma and has potential as a negative prognostic marker. OncoTargets Ther 11:891–901. https://doi.org/10.2147/ott.s154754 CrossRef

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (New York) 235:177–182CrossRef

Takada M et al (2018) Prediction of postoperative disease-free survival and brain metastasis for HER2-positive breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab using a machine learning algorithm. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-018-4958-9 CrossRefPubMed

Tao D, Pan Y, Jiang G, Lu H, Zheng S, Lin H, Cao F (2015) B-Myb regulates snail expression to promote epithelial-to-mesenchymal transition and invasion of breast cancer cell. Med Oncol (Northwood, London, England) 32:412. https://doi.org/10.1007/s12032-014-0412-y CrossRef

Thorner AR, Hoadley KA, Parker JS, Winkel S, Millikan RC, Perou CM (2009) In vitro and in vivo analysis of B-Myb in basal-like breast cancer. Oncogene 28:742–751. https://doi.org/10.1038/onc.2008.430 CrossRefPubMed

Thu KL et al (2018) Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors in triple-negative breast cancer. Proc Natl Acad Sci USA 115:E1570–e1577. https://doi.org/10.1073/pnas.1719577115 CrossRefPubMed

Trainer AH, Thompson E, James PA (2011) BRCA and beyond: a genome-first approach to familial breast cancer risk assessment. Discov Med 12:433–443PubMed

Uhlen M et al (2010) Towards a knowledge-based Human Protein Atlas. Nat Biotechnol 28:1248–1250. https://doi.org/10.1038/nbt1210-1248 CrossRefPubMed

Uhlen M et al (2015) Proteomics. Tissue-based map of the human proteome. Science (New York) 347:1260419. https://doi.org/10.1126/science.1260419 CrossRef

von Minckwitz G et al (2018) Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol 19:987–998. https://doi.org/10.1016/s1470-2045(18)30241-9 CrossRef

Wang J et al (2017) Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition. Cell Cycle (Georget) 16:2355–2365. https://doi.org/10.1080/15384101.2017.1388972 CrossRef

Wang J et al (2018) Silencing of CDCA5 inhibits cancer progression and serves as a prognostic biomarker for hepatocellular carcinoma. Oncol Rep 40:1875–1884. https://doi.org/10.3892/or.2018.6579 CrossRefPubMedPubMedCentral

Yuan B et al (2006) Increased expression of mitotic checkpoint genes in breast cancer cells with chromosomal instability. Clin Cancer Res 12:405–410. https://doi.org/10.1158/1078-0432.Ccr-05-0903 CrossRefPubMed

Zhang H et al (2018a) Acetylation of AGO2 promotes cancer progression by increasing oncogenic miR-19b biogenesis. Oncogene. https://doi.org/10.1038/s41388-018-0530-7 CrossRefPubMedPubMedCentral

Zhang Z, Shen M, Zhou G (2018b) Upregulation of CDCA5 promotes gastric cancer malignant progression via influencing cyclin E1. Biochem Biophys Res Commun 496:482–489. https://doi.org/10.1016/j.bbrc.2018.01.046 CrossRefPubMed

Titel: Co-expression network analysis identified candidate biomarkers in association with progression and prognosis of breast cancer
verfasst von: Qiang Zhou
Jiangbo Ren
Jinxuan Hou
Gang Wang
Lingao Ju
Yu Xiao
Yan Gong
Publikationsdatum: 06.07.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02974-4

Springer Medizin

Co-expression network analysis identified candidate biomarkers in association with progression and prognosis of breast cancer

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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