Duan Ling, Xia Yang, Fan Rui, Shuai Yuxi, Li Chunmei, Hou Xiaoming
Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China.
The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China.
Discov Oncol. 2024 Sep 17;15(1):454. doi: 10.1007/s12672-024-01350-0.
Colorectal cancer (CRC) is characterized by high incidence and mortality rates worldwide. In this study, we present a novel aging-related gene-based risk scoring system (Aging score) as a predictive tool for CRC prognosis.
We identified prognostic aging-related genes using univariate Cox regression analysis, revealing key biological processes in CRC progression. We then constructed a robust prognostic model using LASSO and multivariate Cox regression analyses, including four critical genes: CAV1, FOXM1, MAD2L1, and WT1.
The Aging score demonstrated high prognostic performance across the training, testing, and entire TCGA-CRC datasets, proving its reliability. High-risk patients identified by the Aging score had significantly shorter overall survival times than low-risk patients, indicating its potential for patient stratification and personalized treatment. The Aging score remained an independent prognostic factor compared to age, gender, and tumor stage. Additionally, the score was linked to tumor mutation burden and microsatellite instability, indicators of immune checkpoint inhibitor response. High-risk patients also showed higher estimated IC50 values for common chemotherapeutic drugs, suggesting possible treatment resistance.
Our findings highlight the Aging score's potential to enhance clinical decision-making and pave the way for personalized CRC management.
结直肠癌（CRC）在全球范围内具有高发病率和死亡率的特点。在本研究中，我们提出了一种基于衰老相关基因的新型风险评分系统（衰老评分），作为CRC预后的预测工具。
我们使用单变量Cox回归分析确定预后衰老相关基因，揭示CRC进展中的关键生物学过程。然后，我们使用LASSO和多变量Cox回归分析构建了一个稳健的预后模型，包括四个关键基因：CAV1、FOXM1、MAD2L1和WT1。
衰老评分在训练、测试和整个TCGA-CRC数据集中均表现出较高的预后性能，证明了其可靠性。衰老评分确定的高危患者的总生存时间明显短于低危患者，表明其在患者分层和个性化治疗方面的潜力。与年龄、性别和肿瘤分期相比，衰老评分仍然是一个独立的预后因素。此外，该评分与肿瘤突变负担和微卫星不稳定性相关，这是免疫检查点抑制剂反应的指标。高危患者对常用化疗药物的估计IC50值也较高，表明可能存在治疗耐药性。
我们的研究结果突出了衰老评分在加强临床决策方面的潜力，并为CRC的个性化管理铺平了道路。
