New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses

Caner Karaca, Ezgi Demir Karaman, Asim Leblebici, Hasan Kurter, Hulya Ellidokuz, Altug Koc, Ender Berat Ellidokuz, Zerrin Isik, Yasemin Basbinar

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Metastatic colorectal cancer (CRC) is still in need of effective treatments. This study applies a holistic approach to propose new targets for treatment of primary and liver metastatic CRC and investigates their therapeutic potential in-vitro. An integrative analysis of primary and metastatic CRC samples was implemented for alternative target and treatment proposals. Integrated microarray samples were grouped based on a co-expression network analysis. Significant gene modules correlated with primary CRC and metastatic phenotypes were identified. Network clustering and pathway enrichments were applied to gene modules to prioritize potential targets, which were shortlisted by independent validation. Finally, drug-target interaction search led to three agents for primary and liver metastatic CRC phenotypes. Hesperadin and BAY-1217389 suppress colony formation over a 14-day period, with Hesperadin showing additional efficacy in reducing cell viability within 48 h. As both candidates target the G2/M phase proteins NEK2 or TTK, we confirmed their anti-proliferative properties by Ki-67 staining. Hesperadinin particular arrested the cell cycle at the G2/M phase. IL-29A treatment reduced migration and invasion capacities of TGF-β induced metastatic cell lines. In addition, this anti-metastatic treatment attenuated TGF-β dependent mesenchymal transition. Network analysis suggests IL-29A induces the JAK/STAT pathway in a preventive manner.
Original languageEnglish
Article number8762
JournalScientific Reports
Volume14
Issue number1
DOIs
Publication statusPublished - 1 Dec 2024
Externally publishedYes

Funding

This research was supported by a grant from the TUSEB Scientific Research Project Coordination Unit (Grant Number: 2019.4079).

FundersFunder number
TUSEB2019.4079

    Fingerprint

    Dive into the research topics of 'New treatment alternatives for primary and metastatic colorectal cancer by an integrated transcriptome and network analyses'. Together they form a unique fingerprint.

    Cite this