Faculty of Sciences and Advanced Technologies in Biology, University of Science and Culture, ACECR, Tehran, Iran.
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Mol Biol Rep. 2024 Jun 14;51(1):764. doi: 10.1007/s11033-024-09683-3.
Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic characteristics. CpG island methylator phenotype (CIMP) is found in about 15-20% of sporadic CRCs and is associated with hypermethylation of certain gene promoters. This study aims to find prognostic genes and compare their expression and methylation status as potential biomarkers in patients with serrated sessile adenomas/polyps (SSAP) and CRC, in order to evaluate which, one is a better predictor of disease.
This study employed a multi-phase approach to investigate genes associated with CRC and SSAP. Initially, two gene expression datasets were analyzed using R and Limma package to identify differentially expressed genes (DEGs). Venn diagram analysis further refined the selection, revealing four genes from the Weissenberg panel with significant changes. These genes, underwent thorough in silico evaluations. Once confirmed, they proceeded to wet lab experimentation, focusing on expression and methylation status. This comprehensive methodology ensured a robust examination of the genes involved in CRC and SSAP.
This study identified cancer-specific genes, with 8,351 and 1,769 genes specifically down-regulated in SSAP and CRC tissues, respectively. The down-regulated genes were associated with cell adhesion, negative regulation of cell proliferation, and drug response. Four highly downregulated genes in the Weissenberg panel, including CACNA1G, IGF2, MLH1, and SOCS1. In vitro analysis showed that they are hypermethylated in both SSAP and CRC samples while their expressions decreased only in CRC samples.
This suggests that the decrease in gene expression could help determine whether a polyp will become cancerous. Using both methylation status and gene expression status of genes in the Weissenberg panel in prognostic tests may lead to better prognoses for patients.
结直肠癌（CRC）起源于结肠中预先存在的息肉。不同亚型 CRC 的发展受到各种遗传和表观遗传特征的影响。CpG 岛甲基化表型（CIMP）在约 15-20%的散发性 CRC 中发现，与某些基因启动子的超甲基化有关。本研究旨在寻找预后基因，并比较其在锯齿状无蒂腺瘤/息肉（SSAP）和 CRC 患者中的表达和甲基化状态，作为潜在的生物标志物，以评估哪一种是疾病更好的预测指标。
本研究采用多阶段方法研究与 CRC 和 SSAP 相关的基因。首先，使用 R 和 Limma 包分析了两个基因表达数据集，以鉴定差异表达基因（DEGs）。Venn 图分析进一步细化了选择，从 Weissenberg 面板中发现了四个具有显著变化的基因。这些基因进行了深入的计算机分析。一旦确认，它们就进入了湿实验室实验，重点是表达和甲基化状态。这种全面的方法确保了对涉及 CRC 和 SSAP 的基因进行了稳健的检查。
本研究确定了癌症特异性基因，SSAP 和 CRC 组织中分别有 8351 个和 1769 个基因特异性下调。下调的基因与细胞黏附、细胞增殖的负调控和药物反应有关。Weissenberg 面板中四个高度下调的基因，包括 CACNA1G、IGF2、MLH1 和 SOCS1。体外分析表明，它们在 SSAP 和 CRC 样本中均呈高甲基化状态，而其表达仅在 CRC 样本中降低。
这表明基因表达的降低可以帮助确定息肉是否会癌变。在预后试验中使用 Weissenberg 面板中基因的甲基化状态和基因表达状态可能会为患者带来更好的预后。
