Chen Yu, Jiang Yupeng, Li Xionghui, Huang Hong, Zhou Yangying, Zhang Chenzi, Wang Shunjun, Bohnenberger Hanibal, Gao Yawen
Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Transl Lung Cancer Res. 2024 May 31;13(5):1084-1100. doi: 10.21037/tlcr-24-245. Epub 2024 May 29.
Vitamins, and their metabolic processes play essential regulatory roles in controlling proliferation, differentiation, and growth in carcinogenesis. However, the role of vitamin metabolism in lung adenocarcinoma (LUAD) has rarely been reported. Here, we established a novel prognostic model based on vitamin metabolism-related genes in LUAD.
In this research, we aimed to identify vitamin metabolism associated with differentially expressed genes (DEGs) in LUAD utilizing The Cancer Genome Atlas (TCGA)-LUAD, GSE68465 and GSE72094 data. Unsupervised clustering classified patients into distinct subgroups. By utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, vitamin metabolism-related genes could be used to construct prognostic model. Then the vitamin metabolism gene-related risk score (VRS) was calculated based on best cut-off splitting. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) analysis, univariate and multivariate Cox analyses, chemotherapeutic drugs sensitivity analysis, immune infiltration analysis and nomogram were conducted to verify our models' accuracy. Finally, CPS1 was identified as a relevant diagnostic marker using Random Forests algorithms, single-cell RNA sequencing data was used to confirm its expression.
We investigated the relationship between vitamin metabolism patterns, overall survival (OS), and immune infiltration levels of patients with LUAD. A prognostic signature consisting of 11 genes was developed, which was able to classify patients into high and low VRS groups. Through gene enrichment analysis, cell cycle was mainly enriched. Compared to the low VRS group, the high VRS group exhibited poorer OS, as demonstrated by the Kaplan-Meier survival analysis. Furthermore, VRS was identified as an independent predictor of poor prognosis and poor OS, as indicated by both univariate and multivariate Cox regression analyses. Additionally, a nomogram was constructed to improve the accuracy of survival predictions in LUAD patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CPS1 was identified as a relevant diagnostic marker and the expression was also as confirmed by single-cell RNA sequencing data.
Overall, our findings suggest that vitamin metabolism can influence the prognosis of LUAD patients, and our prognostic signature represents a potentially helpful resource for predicting patient outcomes and informing clinical decision-making.
维生素及其代谢过程在控制癌症发生中的增殖、分化和生长方面发挥着重要的调节作用。然而，维生素代谢在肺腺癌（LUAD）中的作用鲜有报道。在此，我们基于LUAD中与维生素代谢相关的基因建立了一种新的预后模型。
在本研究中，我们旨在利用癌症基因组图谱（TCGA）-LUAD、GSE68465和GSE72094数据，识别与LUAD中差异表达基因（DEG）相关的维生素代谢。无监督聚类将患者分为不同亚组。通过使用最小绝对收缩和选择算子（LASSO）-Cox回归分析，维生素代谢相关基因可用于构建预后模型。然后根据最佳截断分割计算维生素代谢基因相关风险评分（VRS）。进行Kaplan-Meier分析、时间依赖性受试者工作特征（ROC）分析、单因素和多因素Cox分析、化疗药物敏感性分析、免疫浸润分析和列线图分析，以验证我们模型的准确性。最后，使用随机森林算法将CPS1鉴定为相关诊断标志物，利用单细胞RNA测序数据确认其表达。
我们研究了LUAD患者的维生素代谢模式、总生存期（OS）和免疫浸润水平之间的关系。开发了一个由11个基因组成的预后特征，它能够将患者分为高VRS组和低VRS组。通过基因富集分析，主要富集在细胞周期。Kaplan-Meier生存分析表明，与低VRS组相比，高VRS组的OS较差。此外，单因素和多因素Cox回归分析均表明，VRS被确定为预后不良和OS较差的独立预测因子。此外，构建了列线图以提高LUAD患者生存预测的准确性。我们还发现，两组患者对免疫靶点和抗肿瘤药物的反应可能不同。CPS1被鉴定为相关诊断标志物，单细胞RNA测序数据也证实了其表达。
总体而言，我们的研究结果表明，维生素代谢可以影响LUAD患者的预后，我们的预后特征为预测患者预后和指导临床决策提供了一个潜在有用的资源。
