Department of Radiology and Nuclear Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241250285. doi: 10.1177/15330338241250285.
Colorectal cancer is a highly aggressive malignant tumor that primarily affects the digestive system. It is frequently diagnosed at an advanced stage. Cuproptosis is a copper-dependent form cell death mechanism, distinct from all other known pathways underlying cell death, tumor progression, prognosis, and immune response. Although the role of cuproptosis in colorectal cancer has been investigated over time, there is still an urgent need to explore new methods and insights to understand its potential function. The Gene Expression Omnibus and The Cancer Genome Atlas gene expression data were systematically explored to investigate the role of cuproptosis in colon adenocarcinoma. The weighted gene coexpression network analysis was used to construct a gene coexpression network and identify the critical module and cuproptosis-related genes correlated with colon adenocarcinoma prognosis. A cuproptosis-related genes prognostic signature for colon adenocarcinoma was identified and validated. To validate the identified gene signature, quantitative reverse transcription-polymerase chain reaction was performed. Cell proliferation assays were analyzed by CCK8 and cell cycle detection. In addition, reactive oxygen species assay was also analyzed. Five hub cuproptosis-related genes (Dihydrolipoamide S-acetyltransferase, Cyclin-dependent kinase inhibitor 2A, ATOX1, VEGFA, and ULK1) were screened and a prognostic risk model for predicting overall survival was established based on these genes. The model was successfully tested in the validation cohort and the GEPIA database. Colon adenocarcinoma patients were categorized into high-risk and low-risk groups based on risk scores. The study revealed that patients with higher risk scores were more likely to have a poor prognosis. Moreover, Dihydrolipoamide S-acetyltransferase was a tumor suppressor gene that can induce cell death and affected the redox reactions in the colon cancer cell line. These findings suggest that the newly identified 5-gene signature may serve as a more reliable prognostic factor than clinical factors such as age and stage of disease. These findings offer a theoretical foundation for further investigation into potential cuproptosis-related biomarkers for predicting colon adenocarcinoma prognosis in the future.
结直肠癌是一种高度侵袭性的恶性肿瘤，主要影响消化系统。它通常在晚期被诊断出来。铜死亡是一种依赖铜的细胞死亡机制，与所有其他已知的细胞死亡途径、肿瘤进展、预后和免疫反应都不同。虽然铜死亡在结直肠癌中的作用随着时间的推移已经得到了研究，但仍需要探索新的方法和见解来理解其潜在功能。系统地探讨了基因表达综合数据库和癌症基因组图谱基因表达数据，以研究铜死亡在结肠腺癌中的作用。使用加权基因共表达网络分析构建基因共表达网络，并确定与结肠腺癌预后相关的关键模块和铜死亡相关基因。确定并验证了一个与结肠腺癌相关的铜死亡相关基因预后签名。为了验证鉴定的基因特征，进行了定量逆转录聚合酶链反应。通过 CCK8 和细胞周期检测分析细胞增殖实验。此外，还分析了活性氧物质测定。筛选出五个关键的铜死亡相关基因（二氢硫辛酰胺 S-乙酰转移酶、细胞周期蛋白依赖性激酶抑制剂 2A、ATOX1、VEGFA 和 ULK1），并基于这些基因建立了预测总生存期的预后风险模型。该模型在验证队列和 GEPIA 数据库中得到了成功验证。根据风险评分将结肠腺癌患者分为高风险和低风险组。研究表明，风险评分较高的患者预后较差。此外，二氢硫辛酰胺 S-乙酰转移酶是一种肿瘤抑制基因，可诱导细胞死亡，并影响结肠癌细胞系中的氧化还原反应。这些发现表明，新确定的 5 基因特征可能比年龄和疾病分期等临床因素更可靠地作为预后因素。这些发现为进一步研究未来预测结肠腺癌预后的潜在铜死亡相关生物标志物提供了理论基础。
