Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Md. Rezanur Rahman
* ORCID logo ,
Tania Islam
ORCID logo ,
Esra Gov
,
Beste Turanli
ORCID logo ,
Md. Shahjaman
,
Nilufa Akhter Banu
,
Md. Nurul Haque Mollah
,
Kazim Yalcin Arga
ORCID logo ,
Mohammad Ali Moni
*
Version 1 : Received: 30 November 2018 / Approved: 3 December 2018 / Online: 3 December 2018 (09:33:34 CET)
Version 2 : Received: 28 December 2018 / Approved: 29 December 2018 / Online: 29 December 2018 (07:05:05 CET)

A peer-reviewed article of this Preprint also exists.

Rahman, M.R.; Islam, T.; Gov, E.; Turanli, B.; Gulfidan, G.; Shahjaman, M.; Banu, N.A.; Mollah, M.N.H.; Arga, K.Y.; Moni, M.A. Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis. Medicina 2019, 55, 20. Rahman, M.R.; Islam, T.; Gov, E.; Turanli, B.; Gulfidan, G.; Shahjaman, M.; Banu, N.A.; Mollah, M.N.H.; Arga, K.Y.; Moni, M.A. Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis. Medicina 2019, 55, 20.

Abstract

Background and objectives: Colorectal cancer (CRC) is the 2nd most cause of cancer related death in the world, but early diagnosis ameliorates the survival of CRC. This report directed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) to identify common differentially expressed genes (DEGs). We performed functional overrepresentation, pathway enrichment, protein-protein interaction (PPI), reporter biomolecules, survival, and drug repositioning analyses were done on common DEGs. Results: Total 727 up-regulated and 99 down-regulated DEGs were detected. The significantly enriched pathways PI3K-Akt signaling, Wnt signaling, ECM-interaction, cell cycles were identified. The 10 hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2) were selected as proteomic signatures from PPI network. Analyses revealed 10 reporter transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and 2 reporter microRNAs (miR-193b-3p and miR-615-3p) as regulatory component. The prognostic power analysis revealed that hub proteins and reporter biomolecules related with worse survival of patients in CRC. Several candidate repositioned drugs including anti-neoplastic and immunomodulating agents were identified using Connectivity map (CMap) and geneXpharma tool. 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 can be potential biomarkers and therapeutic target in CRC.

Keywords

colorectal cancer; differentially expressed genes; biomarkers; protein-protein interaction; reporter biomolecules; candidate drugs; systems biology; drug repositioning

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (2)

Comment 1
Received: 4 December 2018
Commenter: Gurudeeban Selvaraj
The commenter has declared there is no conflict of interests.
Comment: The article entitled"Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis" is a quite good study. But there are some important critics

1) How the author select microarray datasets? what is the selection criteria?
2) How the authors pre-process their datasets?
3) What is the correlation between the results of DEGs, TFs, and miRNAs?
4) The HR is missing for survival plots
5) How to describe the use of proposing more than one drug for target?
+ Respond to this comment
Response 1 to Comment 1
Received: 15 January 2019
Commenter:
Md Rezanur Rahman

The commenter has declared there is no conflict of interests.
Comment: Dear Dr. Gurudeeban Selvaraj,
Thank you for your valuable comments. We think we have revised sufficiently to addressed the above points. Therefore, the updated version (version 2) included all the points mentioned.
Thank you again.

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