结直肠癌被列为全球第三大常见恶性肿瘤。它的发展涉及由各种遗传和表观遗传改变驱动的复杂的生物过程。为了阐明广泛组学数据的生物学意义，我们对不同临床阶段的结直肠癌患者进行了比较多组学研究。应用生物信息学方法分析多组学数据集并探索分子景观。还进行了药物预测和分子对接，以评估潜在的治疗干预措施。体外实验用于验证对细胞系迁移和增殖的抑制作用。结果表明，参与免疫炎症相关途径的蛋白质上调，而与肌肉收缩和细胞粘附相关的生物标志物显着下调。药物预测结合体外实验表明，AZ-628可能作为一种潜在药物，通过调节上述关键生物途径或蛋白质来抑制CRC细胞系HCT-116和HT-29的增殖和迁移。作为对这些发现的补充，代谢组学分析揭示了关键碳代谢途径的下调，同时氨基酸代谢（特别是脯氨酸代谢）的上调。这种代谢变化可能反映了癌细胞的适应性反应，有利于特定氨基酸支持其生长。总之，这些综合结果为肿瘤发展的复杂景观提供了宝贵的见解，突出了肿瘤发生过程中免疫调节、细胞结构和代谢重编程的十字路口，并为癌症病理学提供了宝贵的见解。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Colorectal cancer is globally ranked as the third most common malignant tumor. Its development involves a complex biological process driven by various genetic and epigenetic alterations. To elucidate the biological significance of the extensive omics data, we conducted comparative multi-omics studies on colorectal cancer patients at different clinical stages. Bioinformatics methods were applied to analyze multi-omics datasets and explore the molecular landscape. Drug prediction and molecular docking also were conducted to assess potential therapeutic interventions. In vitro experiments were used to validate the inhibitory effect on the migration and proliferation of cell lines. The results indicate up-regulated proteins involved in immune-inflammatory related pathways, while biomarkers related to muscular contraction and cell adhesion are significantly down-regulated. Drug prediction, coupled with in vitro experiments, suggests that AZ-628 may act as a potential drug to inhibit the proliferation and migration of CRC cell lines HCT-116 and HT-29 by regulating the aforementioned key biological pathways or proteins. Complementing these findings, metabolomics analysis unveiled a down-regulation of key carbon metabolism pathways, alongside an up-regulation in amino acid metabolism, particularly proline metabolism. This metabolic shift may reflect an adaptive response in cancer cells, favoring specific amino acids to support their growth. Together, these integrated results provide valuable insights into the intricate landscape of tumor development, highlighting the crossroads of immune regulation, cellular structure, and metabolic reprogramming in the tumorigenic process and providing valuable insights into cancer pathology.Copyright © 2024 Elsevier Inc. All rights reserved.