鉴定出一个与 5 种营养素应激相关的基因特征，用于预测结直肠癌的生存情况。
Identification of a 5-Nutrient Stress-Sensitive Gene Signature to Predict Survival for Colorectal Cancer.
机构信息
Department of Cardiovascular Medicine, Liyuan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430071, China.
Department of Gastroenterology, Zhijiang People's Hospital, Yichang 443000, China.
出版信息
Biomed Res Int. 2022 Apr 18;2022:2587120. doi: 10.1155/2022/2587120. eCollection 2022.
BACKGROUND
The high heterogeneity and the complexity of the tumor microenvironment of colorectal cancer (CRC) have enhanced the difficulty of prognosis prediction based on conventional clinical indicators. Recent studies revealed that tumor cells could overcome various nutritional deficiencies by gene regulation and metabolic remodeling. However, whether differentially expressed genes (DEGs) in CRC cells under kinds of nutrient deficiency could be used to predict prognosis remained unveiled.
METHODS
Three datasets (GSE70976, GSE13548, and GSE116087), in which colon cancer cells were, respectively, cultured in serum-free, glucose-free, or glutamine-free medium, were included to delineate the profiles of gene expression by nutrient stress. DEGs were figured out in three datasets, and gene functional analysis was performed. Survival analyses and Cox proportional hazards model were then used to identify nutrient stress sensitive genes in CRC datasets (GSE39582 and TCGA COAD). Then, a 5-gene signature was constructed and the risk scores were also calculated. Survival analyses, cox analyses, and nomogram were applied to predict the prognosis of patients with colorectal cancer. The effectiveness of the risk model was also tested.
RESULTS
A total of 48 genes were found to be dysregulated in serum, glucose, or glutamine-deprived CRC cells, which were mainly enriched in cell cycle and endoplasmic reticulum stress pathways. After further analyses, 5 genes, MCM5, MCM6, CDCA2, GINS2, and SPC25, were identified to be differentially expressed in CRC and be related to prognosis of in CRC datasets. We used the above nutrient stress-sensitive genes to construct a risk scoring model. CRC samples in the datasets were divided into low-risk and high-risk groups. Data showed that higher risk scores were associated with better outcomes and risk scores decreased significantly with tumor procession. Moreover, the risk score could be used to predict the probability of survival based on nomogram.
CONCLUSIONS
The 5-nutrient stress-sensitive gene signature could act as an independent biomarker for survival prediction of CRC patients.
背景
结直肠癌（CRC）的高度异质性和肿瘤微环境的复杂性增加了基于传统临床指标进行预后预测的难度。最近的研究表明，肿瘤细胞可以通过基因调控和代谢重塑来克服各种营养缺乏。然而，CRC 细胞在各种营养缺乏下差异表达的基因（DEGs）是否可用于预测预后仍未被揭示。
方法
纳入了三个数据集（GSE70976、GSE13548 和 GSE116087），分别在无血清、无糖或无谷氨酰胺的培养基中培养结肠癌细胞，以描绘营养应激下的基因表达谱。在三个数据集中找出差异表达基因（DEGs），并进行基因功能分析。然后，在 CRC 数据集（GSE39582 和 TCGA COAD）中使用生存分析和 Cox 比例风险模型来识别对营养压力敏感的基因。然后构建了一个 5 基因特征，并计算了风险评分。应用生存分析、Cox 分析和列线图预测结直肠癌患者的预后。还测试了风险模型的有效性。
结果
在血清、葡萄糖或谷氨酰胺剥夺的 CRC 细胞中发现了总共 48 个基因失调，这些基因主要富集在细胞周期和内质网应激途径中。进一步分析后，在 CRC 数据集中鉴定出 5 个基因（MCM5、MCM6、CDCA2、GINS2 和 SPC25）差异表达，并与 CRC 的预后相关。我们使用上述营养压力敏感基因构建了风险评分模型。在数据集中，CRC 样本被分为低风险和高风险组。数据显示，较高的风险评分与较好的结果相关，并且风险评分随着肿瘤进程显著降低。此外，风险评分可基于列线图用于预测生存概率。
结论
5 个营养压力敏感基因特征可作为 CRC 患者生存预测的独立生物标志物。
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