Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

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dc.authoridTURANLI, Beste/0000-0003-1330-9712
dc.authoridArga, Kazim Yalcin/0000-0002-6036-1348
dc.authoridMoni, Mohammad Ali/0000-0003-0756-1006
dc.authoridIslam, Tania/0000-0002-2254-7758
dc.contributor.authorRahman, Md Rezanur
dc.contributor.authorIslam, Tania
dc.contributor.authorGov, Esra
dc.contributor.authorTuranli, Beste
dc.contributor.authorGulfidan, Gizem
dc.contributor.authorShahjaman, Md
dc.contributor.authorBanu, Nilufa Akhter
dc.date.accessioned2025-01-06T17:37:02Z
dc.date.available2025-01-06T17:37:02Z
dc.date.issued2019
dc.description.abstractBackground and objectives: Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world, but early diagnosis ameliorates the survival of CRC. This report aimed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) from the Gene Expression Omnibus (GEO) to identify mutual differentially expressed genes (DEGs). We integrated DEGs with protein-protein interaction and transcriptional/post-transcriptional regulatory networks to identify reporter signaling and regulatory molecules; utilized functional overrepresentation and pathway enrichment analyses to elucidate their roles in biological processes and molecular pathways; performed survival analyses to evaluate their prognostic performance; and applied drug repositioning analyses through Connectivity Map (CMap) and geneXpharma tools to hypothesize possible drug candidates targeting reporter molecules. Results: A total of 727 upregulated and 99 downregulated DEGs were detected. The PI3K/Akt signaling, Wnt signaling, extracellular matrix (ECM) interaction, and cell cycle were identified as significantly enriched pathways. Ten hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2), 10 transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and two microRNAs (miRNAs) (miR-193b-3p and miR-615-3p) were detected as reporter molecules. The survival analyses through Kaplan-Meier curves indicated remarkable performance of reporter molecules in the estimation of survival probability in CRC patients. In addition, several drug candidates including anti-neoplastic and immunomodulating agents were repositioned. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study might be useful in future studies indenting the development of accurate diagnostic and/or prognostic biomarker screens and efficient therapeutic strategies in CRC.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [116M014, 117S489]; Marmara University Research Fund (BAPKO) [FEN-C-DRP-250816-0417, FEN-C-YLP-170118-0013]; Islamic University
dc.description.sponsorshipWe would like to express our thanks to the Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia, Bangladesh, and the Laboratory of Bioinformatics, Department of Statistics, University of Rajshahi, Bangladesh for providing the bioinformatics laboratory facility. This work was supported by an Islamic University research grant (2017-2018). The financial support to Kazim Yalcin Arga by the Scientific and Technological Research Council of Turkey (TUBITAK) through projects 116M014 and 117S489, and the Marmara University Research Fund (BAPKO) through projects FEN-C-DRP-250816-0417 and FEN-C-YLP-170118-0013 are acknowledged.
dc.identifier.doi10.3390/medicina55010020
dc.identifier.issn1010-660X
dc.identifier.issn1648-9144
dc.identifier.issue1
dc.identifier.pmid30658502
dc.identifier.scopus2-s2.0-85060140336
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/medicina55010020
dc.identifier.urihttps://hdl.handle.net/20.500.14669/2088
dc.identifier.volume55
dc.identifier.wosWOS:000457167700016
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofMedicina-Lithuania
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241211
dc.subjectcolorectal cancer
dc.subjectdifferentially expressed genes
dc.subjectbiomarkers
dc.subjectprotein-protein interaction
dc.subjectreporter biomolecules
dc.subjectcandidate drugs
dc.subjectsystems biology
dc.subjectdrug repositioning
dc.titleIdentification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis
dc.typeArticle

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