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Diabetes-specific Modulation of Peripheral Blood Gene Expression Signatures in Colorectal Cancer

Author(s):

Zsuzsanna Molnár, Zsófia Bánlaki, Anikó Somogyi, Zoltán Herold, Magdolna Herold, András Guttman, Zsolt Rónai and Gergely Keszler*   Pages 1 - 8 ( 8 )

Abstract:


Background Type 2 diabetes (T2DM) and colorectal cancer (CRC) are both known to modulate gene expression patterns in peripheral blood leukocytes (PBLs).

Objective: As T2DM has been shown to increase the incidence of CRC, we were prompted to check whether diabetes affects mRNA signatures in PBLs isolated from CRC patients.

Methods: 22 patients were recruited to the study and classified into four cohorts (healthy controls; T2DM; CRC; CRC and T2DM). Relative expression levels of 573 cell signaling gene transcripts were determined by reverse transcription real-time PCR assays run on low-density OpenArray platforms. Enrichment analysis was performed with the g:GOSt profiling tool to order differentially expressed genes into functional pathways.

Results: 49 genes were found to be significantly up- or downregulated in tumorous diabetic individuals as compared to tumor-free diabetic controls, while 11 transcripts were differentially regulated in patients with CRC versus healthy, tumor-free and non-diabetic controls. Importantly, these gene sets were completely distinct, implying that diabetes exerts profound influence on the transcription of signaling genes in CRC. The top 5 genes showing most significant expression differences in both contexts were PCK2, MAPK9, CCND1, HMBS, TLR3 (p≤0.0040) and CREBBP, PPIA, NFKBIL1, MDM2 and SELPLG (p≤ 0.0121), respectively. Functional analysis revealed that most significantly affected pathways were cytokine, interleukin and PI3K/Akt/mTOR signaling cascades as well as mitotic regulation.

Conclusions: We propose that differentially expressed genes listed above might be potential biomarkers of CRC and should be studied further on larger patient groups. Diabetes might promote colorectal carcinogenesis by impairing signaling pathways in PBLs.

Keywords:

colorectal carcinoma, type 2 diabetes, gene expression, RNA, blood, biomarker

Affiliation:

Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Faculty of Medicine, Semmelweis University, Budapest, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Faculty of Medicine, Semmelweis University, Budapest, 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, 2nd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Research Center for Molecular Medicine, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Faculty of Medicine, Semmelweis University, Budapest, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Faculty of Medicine, Semmelweis University, Budapest



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