Einzeltreffer — DigiBib

Breast cancer (BC) remains the leading cause of cancer-related death in women worldwide. The development of new targeted therapies that may improve patient survival remains an area of growing interest. This study aimed to identify new biomarkers involved in BC progression that could be used as potential targeted therapies. DEGs were selected from three gene expression profiles, GSE55715, GSE124646, and GSE87049, using the GEO2R tool and Venn diagram software. Gene Ontology and KEGG pathways were then performed using DAVID software. Next, the PPI network was constructed using STRING and visualized using Cytoscape software, and hub genes were extracted using the cytoHubba plug-in. Survival analysis was performed using the Kaplan-Meier Plotter, while the expression of hub genes in BC was verified using the GEPIA2 tool. Finally, transcription the factors of hub genes were determined using the NetworkAnalyst database, and the TIMER tool was employed to explore the infiltration levels of tumor immune cells with related genes. A total of 146 DEGs were identified in the three datasets, including 60 upregulated genes that were enriched in the cell cycle, and 86 downregulated genes that were mainly enriched in the TNF signaling pathway and pathways in cancer. Ten genes were identified: BUB1, CDK1, HMMR, MAD2L1, CEP55, AURKA, CCNB2, TPX2, MELK, and KIF20A. The overexpression of hub genes, except CDK1, was associated with poor survival in BC and was regulated by several transcription factors involved in DNA binding activity and transcription regulation. The infiltration levels of immune cells were positively correlated with hub genes, particularly macrophages and CD4+ T cells. This study identified new reliable molecular biomarkers that can serve as potential therapeutic targets for BC treatment.

Competing Interests: The authors have no funding and conflicts of interest to disclose.

Titel:	Screening of potential hub genes and key pathways associated with breast cancer by bioinformatics tools.
Autor/in / Beteiligte Person:	Oumeddour, A
Link:	Zum Volltext
Zeitschrift:	Medicine, Jg. 102 (2023-03-17), Heft 11, S. e33291
Veröffentlichung:	Hagerstown, Md : Lippincott Williams & Wilkins, 2023
Medientyp:	academicJournal
ISSN:	1536-5964 (electronic)
DOI:	10.1097/MD.0000000000033291
Schlagwort:	Humans Female Gene Expression Profiling Early Detection of Cancer Transcriptome Cell Cycle Proteins genetics Computational Biology Gene Expression Regulation, Neoplastic genetics Protein Serine-Threonine Kinases genetics Breast Neoplasms genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Medicine (Baltimore)] 2023 Mar 17; Vol. 102 (11), pp. e33291. MeSH Terms: Breast Neoplasms* / genetics ; Humans ; Female ; Gene Expression Profiling ; Early Detection of Cancer ; Transcriptome ; Cell Cycle Proteins / genetics ; Computational Biology ; Gene Expression Regulation, Neoplastic / genetics ; Protein Serine-Threonine Kinases / genetics References: Libson S, Lippman M. A review of clinical aspects of breast cancer. Int Rev Psychiatry. 2014;26:4–15. ; Goldhirsch A, Winer EP, Coates AS, et al.; Panel members. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23. ; Alhammad R. Bioinformatics identification of TUBB as potential prognostic biomarker for worse prognosis in ERα-positive and better prognosis in ERα-negative breast cancer. Diagnostics (Basel). 2022;12:2067. ; Lev S. Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis. Biochem Soc Trans. 2020;48:657–65. ; Mehmood S, Faheem M, Ismail H, et al. Breast cancer resistance likelihood and personalized treatment through integrated multiomics. Front Mol Biosci. 2022;9:783494. ; Wang J, Dean DC, Hornicek FJ, et al. RNA sequencing (RNA-Seq) and its application in ovarian cancer. Gynecol Oncol. 2019;152:194–201. ; Cheng YH, Chen YC, Lin E, et al. Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells. Nat Commun. 2019;10:2163. ; Yang X, Kui L, Tang M, et al. High-throughput transcriptome profiling in drug and biomarker discovery. Front Genet. 2020;11:19. ; Kui L, Kong Q, Yang X, et al. High-throughput in vitro gene expression profile to screen of natural herbals for breast cancer treatment. Front Oncol. 2021;11:684351. ; Barrett T, Wilhite SE, Ledouxet P, et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res. 2013;41:D991–5. ; Feng H, Gu ZY, Li Q, et al. Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis. J Ovarian Res. 2019;12:35. ; Wang Z, Meng L, Shan J, et al. To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology. Medicine (Baltimore). 2022;101:e29729. ; Chin CH, Chen SH, Wu HH, et al. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(Suppl 4):S11. ; Tian L, Liao Y. Identification of G6PC as a potential prognostic biomarker in hepatocellular carcinoma based on bioinformatics analysis. Medicine (Baltimore). 2022;101:e29548. ; Tang Z, Kang B, Li C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556–60. ; Zhou G, Soufan O, Ewald J, et al. NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 2019;47:W234–41. ; Yang X, Yang F, Lan L, et al. Potential value of PRKDC as a therapeutic target and prognostic biomarker in pan-cancer. Medicine (Baltimore). 2022;101:e29628. ; Jin G, Wang W, Cheng P, et al. DNA replication and sister chromatid cohesion 1 promotes breast carcinoma progression by modulating the Wnt/β-catenin signaling and p53 protein. J Biosci. 2020;45:127. ; Jamasbi E, Hamelian M, Hossain MA, et al. The cell cycle, cancer development and therapy. Mol Biol Rep. 2022;49:10875–83. ; Maiato H, Gomes AM, Sousa F, et al. Mechanisms of chromosome congression during mitosis. Biology (Basel). 2017;6:13. ; Wang I, Thomas HR, Chen Y, et al. Reduced sister chromatid cohesion acts as a tumor penetrance modifier. PLoS Genet. 2022;18:e1010341. ; Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2022;23:74–88. ; Parida S, Sharma D. The microbiome-estrogen connection and breast cancer risk. Cells. 2019;8:1642. ; Mohanty SS, Mohanty PK. Obesity as potential breast cancer risk factor for postmenopausal women. Genes Dis. 2019;8:117–23. ; Hirata M, Shinden Y, Nagataet A, et al. Clinical features of breast cancer patients with human T-cell lymphotropic virus type-1 infection. Asian Pac J Cancer Prev. 2019;20:1909–12. ; Lin X, Zhou M, Xu Z, et al. Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma. Sci Prog. 2021;104:368504211018053. ; Carvalho AM, Soares da Costa D, Reis RL, et al. RHAMM expression tunes the response of breast cancer cell lines to hyaluronan. Acta Biomater. 2022;146:187–96. ; Jeffery J, Sinha D, Srihari S, et al. Beyond cytokinesis: the emerging roles of CEP55 in tumorigenesis. Oncogene. 2016;35:683–90. ; Huang Y, Guo W, Kan H. TPX2 is a prognostic marker and contributes to growth and metastasis of human hepatocellular carcinoma. Int J Mol Sci. 2014;15:18148–61. ; Yang Y, Li DP, Shen N, et al. TPX2 promotes migration and invasion of human breast cancer cells. Asian Pac J Trop Med. 2015;8:1064–70. ; Mateo F, He Z, Mei L, et al. Modification of BRCA1-associated breast cancer risk by HMMR overexpression. Nat Commun. 2022;13:1895. ; Giuliano CJ, Lin A, Smith JC, et al. MELK expression correlates with tumor mitotic activity but is not required for cancer growth. Elife. 2018;7:e32838. ; Wang Z, Katsaros D, Shen Y, et al. Biological and clinical significance of MAD2L1 and BUB1, genes frequently appearing in expression signatures for breast cancer prognosis. PLoS One. 2015;10:e0136246. ; Zhu XF, Yi M, He J, et al. Pathological significance of MAD2L1 in breast cancer: an immunohistochemical study and meta analysis. Int J Clin Exp Pathol. 2017;10:9190–201. ; Kahl I, Mense J, Finke C, et al. The cell cycle-related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients. J Cell Biochem. 2022;123:581–600. ; Du R, Huang C, Liu K, et al. Targeting AURKA in cancer: molecular mechanisms and opportunities for cancer therapy. Mol Cancer. 2021;20:15. ; Wang X, Xiao H, Wu D, et al. miR-335-5p regulates cell cycle and metastasis in lung adenocarcinoma by targeting CCNB2. Onco Targets Ther. 2020;13:6255–63. ; Moradpoor R, Zali H, Gharebaghian A, et al. Identification of CCNB2 as a potential non-invasive breast cancer biomarker in peripheral blood mononuclear cells using the systems biology approach. Cell J. 2021;23:406–13. ; Xu L, Xia C, Sheng F, et al. CEP55 promotes the proliferation and invasion of tumour cells via the AKT signalling pathway in osteosarcoma. Carcinogenesis. 2018;39:623–31. ; Wang Y, Lee YM, Baitsch L, et al. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2014;3:e01763. ; Xiong M, Zhuang K, Luo Y, et al. KIF20A promotes cellular malignant behavior and enhances resistance to chemotherapy in colorectal cancer through regulation of the JAK/STAT3 signaling pathway. Aging (Milano). 2019;11:11905–21. ; Steven A, Seliger B. The role of immune escape and immune cell infiltration in breast cancer. Breast Care. 2018;13:16–21. ; Burugu S, Asleh-Aburaya K, Nielsen TO. Immune infiltrates in the breast cancer microenvironment: detection, characterization and clinical implication. Breast Cancer. 2017;24:3–15. ; Ostrand-Rosenberg S. Immune surveillance: a balance between protumor and antitumor immunity. Curr Opin Genet Dev. 2008;18:11–8. ; Goff SL, Danforth DN. The role of immune cells in breast tissue and immunotherapy for the treatment of breast cancer. Clin Breast Cancer. 2021;21:e63–73. ; Yang GJ, Zhu MH, Lu XJ, et al. The emerging role of KDM5A in human cancer. J Hematol Oncol. 2021;14:30. ; Boysen G, Rodrigues DN, Rescigno P, et al. SPOP-mutated/CHD1-deleted lethal prostate cancer and abiraterone sensitivity. Clin Cancer Res. 2018;24:5585–93. Substance Nomenclature: 0 (Cell Cycle Proteins) ; EC 2.7.1.- (MELK protein, human) ; EC 2.7.11.1 (Protein Serine-Threonine Kinases) ; 0 (Cep55 protein, human) Entry Date(s): Date Created: 20230317 Date Completed: 20230321 Latest Revision: 20230916 Update Code: 20240513 PubMed Central ID: PMC10019133

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Screening of potential hub genes and key pathways associated with breast cancer by bioinformatics tools.