Ivonne Wence-Chavez Laura, Palomares-Chacon Ulises, Pablo Flores-Gutierrez Juan, Felipe Jave-Suarez Luis, Del Carmen Aguilar-Lemarroy Adriana, Barros-Nunez Patricio, Esperanza Flores-Martinez Silvia, Sanchez-Corona Jose, Alejandra Rosales-Reynoso Monica
Doctorate Program in Molecular Biology, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.
J BUON. 2017 Sep-Oct;22(5):1107-1114.
Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM.
In this study, microarray analysis of gene expression followed by quantitative PCR (qPCR) was performed in cancer tissue from CRC patients with and without DM to identify the gene expression profiles and validate the differently expressed genes.
Among the study groups, some differently expressed genes were identified. However, when bioinformatics clustering tools were used, a significant modulation of genes involved in the WNT pathway was evident. Therefore, we focused on genes participating in this pathway, such as WNT3A, LRP6, TCF7L2, and FRA-1. Validation of the expression levels of those genes by qPCR showed that CRC patients without type 2 diabetes mellitus (T2DM) expressed significantly more WNT3Ay LRP6, but less TCF7L2 and FRA-1 compared to controls, while in CRC patients with DM the expression levels of WNT3A, LRP6, TCF7L2, and FRA-1 were significantly higher compared to controls.
Our results suggest that WNT/β-catenin pathway is upregulated in patients with CRC and DM, demonstrating its importance and involvement in both pathologies.
多项研究表明，糖尿病（DM）与结直肠癌（CRC）风险增加之间存在密切关联。支持这种关联的基本机制尚未完全明确；然而，人们认为高胰岛素血症和高血糖可能与之有关。一些提出的机制包括有丝分裂信号通路如MAPK、PI3K、mTOR和WNT的上调，这些通路参与细胞增殖、生长和癌细胞存活。本研究的目的是评估基因表达谱，并确定在患有和未患有DM的CRC患者中参与有丝分裂途径的差异表达基因。
在本研究中，对患有和未患有DM的CRC患者的癌组织进行基因表达微阵列分析，随后进行定量PCR（qPCR），以确定基因表达谱并验证差异表达基因。
在研究组中，鉴定出了一些差异表达基因。然而，当使用生物信息学聚类工具时，WNT通路相关基因的显著调节是明显的。因此，我们专注于参与该通路的基因，如WNT3A、LRP6、TCF7L2和FRA-1。通过qPCR对这些基因表达水平的验证表明，与对照组相比，非2型糖尿病（T2DM）的CRC患者表达的WNT3A和LRP6明显更多，但TCF7L2和FRA-1更少，而在患有DM的CRC患者中，WNT3A、LRP6、TCF7L2和FRA-1的表达水平与对照组相比显著更高。
我们的结果表明，WNT/β-连环蛋白通路在患有CRC和DM的患者中上调，证明了其在这两种疾病中的重要性和参与情况。
