Li Miaomiao, Zhang Tianyang, Chen Wei
School of Life Sciences, North China University of Science and Technology, Tangshan, China.
Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Genet. 2022 Oct 24;13:1051800. doi: 10.3389/fgene.2022.1051800. eCollection 2022.
Colon adenocarcinoma (COAD) is a common malignancy and has a high mortality rate. However, the current tumor node metastasis (TNM) staging system is inadequate for prognostic assessment of COAD patients. Therefore, there is an urgent need to identify reliable biomarkers for the prognosis COAD patients. The aberrant expression of necroptosis-related genes (NRGs) is reported to be associated with tumorigenesis and metastasis. In the present work, we compared the expression profiles of NRGs between COAD patients and normal individuals. Based on seven differentially expressed NRGs, a risk score was defined to predict the prognosis of COAD patients. The validation results from both training and independent external cohorts demonstrated that the risk score is able to distinguish the high and low risk COAD patients with higher accuracies, and is independent of the other clinical factors. To facilitate its clinical use, by integrating the proposed risk score, a nomogram was built to predict the risk of individual COAD patients. The C-index of the nomogram is 0.75, indicating the reliability of the nomogram in predicting survival rates. Furthermore, two candidate drugs, namely dapsone and xanthohumol, were screed out and validated by molecular docking, which hold the potential for the treatment of COAD. These results will provide novel clues for the diagnosis and treatment of COAD.
结肠腺癌（COAD）是一种常见的恶性肿瘤，死亡率很高。然而，目前的肿瘤淋巴结转移（TNM）分期系统不足以对COAD患者进行预后评估。因此，迫切需要为COAD患者的预后鉴定可靠的生物标志物。据报道，坏死性凋亡相关基因（NRGs）的异常表达与肿瘤发生和转移有关。在本研究中，我们比较了COAD患者和正常个体之间NRGs的表达谱。基于七个差异表达的NRGs，定义了一个风险评分来预测COAD患者的预后。来自训练队列和独立外部队列的验证结果表明，该风险评分能够以更高的准确性区分高风险和低风险的COAD患者，并且独立于其他临床因素。为了便于其临床应用，通过整合所提出的风险评分，构建了一个列线图来预测个体COAD患者的风险。列线图的C指数为0.75，表明列线图在预测生存率方面的可靠性。此外，筛选出两种候选药物，即氨苯砜和黄腐酚，并通过分子对接进行了验证，它们具有治疗COAD的潜力。这些结果将为COAD的诊断和治疗提供新的线索。
