YTHDF1和WTAP基因在丽水市结直肠癌中的m6A甲基化修饰对肿瘤分化的影响研究

Investigation of the Impact of m6A Methylation Modifications of YTHDF1 and WTAP Genes on Tumor Differentiation in Colorectal Cancer in Lishui City

摘要: 目的：目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证，探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法：利用生物信息学，我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p < 0.05)。在现实世界中，我们使用定量PCR (Q-PCR)来测量这四个基因在丽水地区结直肠癌及癌旁中的mRNA表达。应用SPSS软件进行多变量逻辑回归分析，我们发现这YTHDF1和WTAP基因mRNA表达水平与结直肠癌分化进程相关。通过免疫组化，我们检查了相应的蛋白表达，并使用Image J进行量化，结果显示，YTHDF1蛋白的表达水平与结直肠癌分化进程呈显著负相关；WTAP蛋白表达水平与结直肠癌分化进程呈显著正相关。此外，我们进行了多变量Cox回归分析，以识别与结直肠癌发生相关的潜在影响因素。结果：在中国丽水地区，YTHDF1蛋白表达与结直肠癌的分化水平呈负相关；WTAP的蛋白表达与结直肠癌的分化水平呈正相关。年龄和饮酒史是结直肠癌发病的关键因素，与性别吸烟无显著关联。GO富集分析表明，YTHDF1和WTAP可能通过参与mRNA修饰、翻译调控和RNA稳定性等机制，进而调控结直肠癌的分化过程。此外，三年内低分化组观察到疾病进展率(TTP)100%和总生存期率(OS)达到0%。结论：在丽水市，YTHDF1和WTAP蛋白影响结直肠癌分化，可能是结直肠癌患者的重要治疗靶点和生物诊断标志物。

Abstract: Background: The role of m6A methylation genes in the differentiation of colorectal cancer is currently unclear. This study combines bioinformatics analysis and experimental validation to explore the expression patterns of these genes in colorectal cancer and their potential mechanisms. Methods: Using bioinformatics, we found that YTHDF1, YTHDF2, ALKBH5, and WTAP are significantly aberrantly expressed in colorectal cancer (p < 0.05). In a real-world cohort from Lishui, quantitative PCR (qPCR) was used to measure mRNA expression of these four genes in CRC tissues and adjacent normal tissues. Multivariable logistic regression analysis with SPSS identified YTHDF1 and WTAP mRNA expression levels as being associated with CRC differentiation. Immunohistochemistry (IHC) was performed to examine corresponding protein levels, quantified using ImageJ. Results showed that YTHDF1 protein expression negatively correlated with CRC differentiation, whereas WTAP protein expression positively correlated. Additionally, multivariable Cox regression analysis was conducted to identify potential factors influencing CRC development. Results: In Lishui, YTHDF1 protein expression was negatively associated with CRC differentiation, while WTAP protein expression was positively associated. Age and alcohol consumption were key risk factors for CRC development, while no significant associations were found with sex or smoking. GO enrichment analysis suggests that YTHDF1 and WTAP may regulate the differentiation process of colorectal cancer by participating in mechanisms such as mRNA modification, translation regulation, and RNA stability. For the poorly differentiated CRC group, time to progression rate (TTP) was 100% and overall survival rate (OS) was 0% within three years. Conclusions: In Lishui City, the YTHDF1 and WTAP genes influence the differentiation of colorectal cancer and may serve as important therapeutic targets and biomarkers for the diagnosis of patients with colorectal cancer.