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Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis.
- Source :
-
Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2019 Jan 17; Vol. 55 (1). Date of Electronic Publication: 2019 Jan 17. - Publication Year :
- 2019
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Abstract
- 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. 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 proteinā»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. 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 Kaplanā»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. 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.<br />Competing Interests: The authors declare no conflicts of interest.
- Subjects :
- Antineoplastic Agents therapeutic use
Colorectal Neoplasms genetics
Colorectal Neoplasms mortality
Databases, Genetic
Early Diagnosis
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Immunologic Factors therapeutic use
Kaplan-Meier Estimate
Prognosis
Signal Transduction
Survival Analysis
Systems Biology methods
Biomarkers, Tumor genetics
Colorectal Neoplasms diagnosis
Colorectal Neoplasms drug therapy
ELAV-Like Protein 2 genetics
Genes, Regulator genetics
Genes, Reporter genetics
MicroRNAs genetics
Molecular Targeted Therapy
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1648-9144
- Volume :
- 55
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Medicina (Kaunas, Lithuania)
- Publication Type :
- Academic Journal
- Accession number :
- 30658502
- Full Text :
- https://doi.org/10.3390/medicina55010020