研究动态
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铜凋亡相关基因与结直肠癌预后及肿瘤微环境浸润的综合分析

Comprehensive analysis of cuproptosis-related genes involved in prognosis and tumor microenvironment infiltration of colorectal cancer.

发表日期:2024 Sep 30
作者: Weiyi Chen, Ke Hu, Yu Liu, Xiaocheng Li, Lijun Chen, Shaoyi Duan, Qizhang Yang
来源: Cell Death & Disease

摘要:

结直肠癌(CRC)是一种常见的恶性肿瘤,发病率高、死亡率高。铜中毒是铜诱导的程序性细胞死亡的一种新形式,有助于肿瘤进展。然而,铜凋亡相关基因(CRG)是否在结直肠癌中发挥作用仍不清楚。本研究旨在阐明CRGs在CRC发生、患者预后和免疫反应中的作用。我们对CRC与正常组织之间CRGs的差异表达进行了生物信息学分析。采用最小绝对收缩和选择算子(LASSO)以及单变量和多变量Cox分析来识别风险因素,并用于构建风险评分模型。根据中位风险评分,CRC 患者被分为高风险组和低风险组。采用受试者工作特征曲线分析来验证风险模型的预测准确性。通过单变量和多变量 Cox 回归分析,开发了 CRC 列线图。使用 Wilcoxon 秩和检验比较 CDKN2A/DLAT 高表达和低表达患者之间的化疗药物敏感性。进行Spearman相关性和TISIDB数据库分析以确定CDKN2A或DLAT与免疫细胞浸润之间的关系。十个已识别的CRG中有八个在CRC和正常组织之间表现出显着的差异表达。在八个显着差异表达的 CRG 中,CDKN2A 和 DLAT 被确定为预测 CRC 总生存期 (OS) 的独立危险因素。低风险组的 CRC 患者比高风险组的 OS 更长。风险评分模型对 OS 具有良好的预测准确性。基于CDKN2A、DLAT和一些临床特征,开发了预后列线图来预测CRC患者的OS,并显示出良好的预测能力。 CDKN2A和DLAT的表达与CRC的化疗药物敏感性和免疫细胞浸润显着相关,并且CDKN2A和DLAT之间的分子亚型和免疫亚型存在差异。我们的研究揭示了CRG,特别是CDKN2A和DLAT在CRC中的预后价值,并证明了CDKN2A/DLAT 与 CRC 免疫浸润之间的关系,从而有助于 CRC 患者的结果评估并确定 CRC 免疫治疗的新靶点。2024 AME 出版公司。版权所有。
Colorectal cancer (CRC) is a common malignancy, with high incidence and high mortality rates. Cuproptosis, a novel form of copper-induced programmed cell death, contributes to tumor progression. However, whether cuproptosis-related genes (CRGs) play a role in CRC remains unclear. This study aims to elucidate the role of CRGs in CRC development, patient prognosis, and immune response.We performed bioinformatics analysis of the differential expression of CRGs between CRC and normal tissues. Least absolute shrinkage and selection operator (LASSO), and univariate and multivariate Cox analyses were employed to identify risk factors, which were used to construct a risk score model. Patients with CRC were categorized into high- and low-risk groups based on their median risk scores. Receiver operating characteristic curve analysis was used to verify the predictive accuracy of the risk model. A nomogram was developed for CRC through univariate and multivariate Cox regression analyses. The chemotherapeutic drug sensitivity was compared between patients with high and low CDKN2A/DLAT expression using the Wilcoxon rank-sum test. Spearman's correlation and TISIDB database analyses were conducted to determine relationships between CDKN2A or DLAT and immune cell infiltration.Eight of ten identified CRGs exhibited significant differential expression between CRC and normal tissues. Among the eight significant differential expression CRGs, CDKN2A and DLAT were identified as independent risk factors for predicting overall survival (OS) in CRC. Patients with CRC in the low-risk group had longer OS than those in the high-risk group. The risk score model had good predictive accuracy for OS. Based on CDKN2A, DLAT and some clinical characteristics, a prognostic nomogram was developed to predict OS for CRC patients and showed good predictive ability. CDKN2A and DLAT expressions were significantly associated with chemotherapeutic drug sensitivity and immune cell infiltration in CRC, and the molecular subtypes and immune subtypes differed between CDKN2A and DLAT.Our research revealed the prognostic value of CRGs, particularly CDKN2A and DLAT, in CRC and demonstrated the relationship between CDKN2A/DLAT and immune infiltration in CRC, thereby contributing to the outcome evaluation of patients with CRC and identifying novel targets for CRC immunotherapy.2024 AME Publishing Company. All rights reserved.