Department of Thoracic Surgery, Jinshan Hospital of Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai 200540, China.
Department of Cardiology, Jinshan Hospital of Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai 200540, China.
Dis Markers. 2022 Aug 22;2022:3201600. doi: 10.1155/2022/3201600. eCollection 2022.
The mitochondrial energy metabolic pathway (MEMP) is the primary energy metabolism of tumor cells, and its disruption may promote cancer emergence, spreading, and immune escape. However, there is a lack of studies to determine the relationship between relevant functional mechanisms and lung adenocarcinoma (LUAD) prognosis.
Gene set enrichment analysis (GSEA) was employed to determine MEMP pathway-related genes. Then, a prognostic model was created using the MEMP key genes that were found by LASSO-Cox regression analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided the training and validation sets. Furthermore, the infiltration of immune cells was examined by ssGSEA. Finally, a screening of candidate therapeutic compounds for LUAD patients was performed using DrugBank, Protein Data Bank (PDB), and AutoDock Vina databases.
First, 266 MEMP pathway-related genes that exhibited aberrant activity in tumors were identified. Then, 19 MEMP key genes were used to build a prognostic model, which can successfully predict the survival rates of LUAD patients after 1, 3, and 5 years, respectively. The Kaplan-Meier curve showed that patients in the high-risk group had considerably lower survival outcomes than those in the low-risk group. Furthermore, it was discovered that the high-risk group had the majority of activated T cells, while the low-risk group tended to have more other activated immune cells. The majority of immunological checkpoints expressed themselves more strongly in the high-risk group as well. Finally, 11 prospective medication small molecules were obtained from the projected potential therapeutic drugs, with DB0980 being regarded as the most promising of them for the treatment of LUAD.
This current study developed reliable prognostic signature, called MEMP score, which provides new guidance for prognostic assessment, immunotherapy, and drug development in LUAD. Thereby, DB0980 appears to be the most likely approach for the treatment of LUAD.
线粒体能量代谢途径（MEMP）是肿瘤细胞的主要能量代谢途径，其破坏可能促进癌症的发生、扩散和免疫逃逸。然而，目前缺乏研究来确定相关功能机制与肺腺癌（LUAD）预后之间的关系。
采用基因集富集分析（GSEA）确定 MEMP 途径相关基因。然后，使用 LASSO-Cox 回归分析发现的 MEMP 关键基因构建预后模型。癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）提供了训练和验证集。此外，通过 ssGSEA 检测免疫细胞的浸润情况。最后，使用 DrugBank、蛋白质数据库（PDB）和 AutoDock Vina 数据库筛选 LUAD 患者的候选治疗化合物。
首先，确定了 266 个在肿瘤中表现出异常活性的 MEMP 途径相关基因。然后，使用 19 个 MEMP 关键基因构建了一个预后模型，该模型可以成功预测 LUAD 患者在 1、3 和 5 年后的生存率。Kaplan-Meier 曲线表明，高危组患者的生存结果明显低于低危组。此外，还发现高危组中激活的 T 细胞较多，而低危组中则倾向于有更多其他激活的免疫细胞。高危组中大多数免疫检查点的表达也更强。最后，从预测的潜在治疗药物中获得了 11 种有前景的药物小分子，其中 DB0980 被认为是治疗 LUAD 的最有希望的药物之一。
本研究构建了可靠的预后标志物 MEMP 评分，为 LUAD 的预后评估、免疫治疗和药物开发提供了新的指导。因此，DB0980 似乎是治疗 LUAD 的最有希望的方法。
