摘要
背景:2型糖尿病(T2DM)和结直肠癌(CRC)均可调节外周血白细胞(PBLs)的基因表达模式。 目的:由于T2DM已被证明会增加结直肠癌的发生率,我们被要求检查糖尿病是否会影响从结直肠癌患者中分离出来的PBLs的mRNA鲜明特征。 方法:研究招募了22名患者,并将其分为4组(健康对照组;2型糖尿病;儿童权利公约;CRC和2型糖尿病)。通过低密度OpenArray平台上的逆转录实时荧光定量PCR检测573个细胞信号基因转录本的相对表达水平。利用g:GOSt分析工具进行富集分析,将差异表达基因排列到功能通路中。 结果:与无肿瘤糖尿病对照组相比,49个基因在肿瘤糖尿病个体中显著上调或下调,而11个转录本在CRC患者与健康、无肿瘤和非糖尿病对照组中差异调控。重要的是,这些基因是完全不同的,这意味着糖尿病对CRC信号基因的转录有深远的影响。在两种环境中表达差异最显著的前5个基因分别是PCK2、MAPK9、CCND1、HMBS、TLR3 (p≤0.0040)和CREBBP、PPIA、NFKBIL1、MDM2和SELPLG (p≤0.0121)。功能分析表明,细胞因子、白细胞介素和PI3K/Akt/mTOR信号级联以及有丝分裂调控是最显著的通路。 结论:我们认为上述差异表达基因可能是CRC的潜在生物标志物,需要在更大的患者群体中进行进一步研究。糖尿病可能通过损害PBLs信号通路促进结直肠癌的发生。
关键词: 结直肠癌,2型糖尿病,基因表达,RNA,血液,生物标志物
Current Molecular Medicine
Title:Diabetes-specific Modulation of Peripheral Blood Gene Expression Signatures in Colorectal Cancer
Volume: 20 Issue: 10
关键词: 结直肠癌,2型糖尿病,基因表达,RNA,血液,生物标志物
摘要:
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: Twenty-two 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 nondiabetic controls. Importantly, these gene sets were completely distinct, implying that diabetes exerts a profound influence on the transcription of signaling genes in CRC. The top 5 genes showing the 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.
Conclusion: 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.
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Cite this article as:
Diabetes-specific Modulation of Peripheral Blood Gene Expression Signatures in Colorectal Cancer, Current Molecular Medicine 2020; 20 (10) . https://dx.doi.org/10.2174/1566524020666200504084626
DOI https://dx.doi.org/10.2174/1566524020666200504084626 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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